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Sample records for long-term potentiation induction

  1. Stochastic Induction of Long-Term Potentiation and Long-Term Depression

    PubMed Central

    Antunes, G.; Roque, A. C.; Simoes-de-Souza, F. M.

    2016-01-01

    Long-term depression (LTD) and long-term potentiation (LTP) of granule-Purkinje cell synapses are persistent synaptic alterations induced by high and low rises of the intracellular calcium ion concentration ([Ca2+]), respectively. The occurrence of LTD involves the activation of a positive feedback loop formed by protein kinase C, phospholipase A2, and the extracellular signal-regulated protein kinase pathway, and its expression comprises the reduction of the population of synaptic AMPA receptors. Recently, a stochastic computational model of these signalling processes demonstrated that, in single synapses, LTD is probabilistic and bistable. Here, we expanded this model to simulate LTP, which requires protein phosphatases and the increase in the population of synaptic AMPA receptors. Our results indicated that, in single synapses, while LTD is bistable, LTP is gradual. Ca2+ induced both processes stochastically. The magnitudes of the Ca2+ signals and the states of the signalling network regulated the likelihood of LTP and LTD and defined dynamic macroscopic Ca2+ thresholds for the synaptic modifications in populations of synapses according to an inverse Bienenstock, Cooper and Munro (BCM) rule or a sigmoidal function. In conclusion, our model presents a unifying mechanism that explains the macroscopic properties of LTP and LTD from their dynamics in single synapses. PMID:27485552

  2. Metabotropic glutamate receptors are required for the induction of long-term potentiation

    NASA Technical Reports Server (NTRS)

    Zheng, F.; Gallagher, J. P.

    1992-01-01

    Recent observations have led to the suggestion that the metabotropic glutamate receptor may play a role in the induction or maintenance of long-term potentiation (LTP). However, experimental evidence supporting a role for this receptor in the induction of LTP is still inconclusive and controversial. Here we report that, in rat dorsolateral septal nucleus (DLSN) neurons, which have the highest density of metabotropic receptors and show functional responses, the induction of LTP is not blocked by the NMDA receptor antagonist 2-amino-5-phosphonovalerate, but is blocked by two putative metabotropic glutamate receptor antagonists, L-2-amino-3-phosphonopropionic acid and L-2-amino-4-phosphonobutyrate. Furthermore, superfusion of (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid, a selective metabotropic glutamate agonist, resulted in a long-lasting potentiation of synaptic transmission similar to that induced by tetanic stimuli. Our results demonstrated that activation of postsynaptic metabotropic receptors is both necessary and sufficient for the induction of LTP in the DLSN, and we suggest that such a mechanism may be important at other CNS synapses.

  3. Oxytocin facilitates the induction of long-term potentiation in the accessory olfactory bulb.

    PubMed

    Fang, Long-Yun; Quan, Rong-Dan; Kaba, Hideto

    2008-06-20

    When female mice are mated, they form a memory to the pheromonal signal of their male partner. Several lines of evidence indicate that the neural changes underlying this memory occur in the accessory olfactory bulb (AOB) at the first stage of the vomeronasal system. The formation of this memory depends on the mating-induced release of noradrenaline in the AOB. In addition to noradrenaline, the neuropeptide oxytocin (OT) is also released within the central nervous system during mating. Because OT has been implicated in social memory and its receptors are expressed in the AOB, we hypothesized that OT might promote the strength of synaptic transmission from mitral to granule cells in the AOB. To test this hypothesis, we analyzed the lateral olfactory tract-evoked field potential that represents the granule cell response to mitral cell activation and its plasticity in parasagittal slices of the AOB. Of the 10-, 20-, 50-, and 100-Hz stimulations tested, the 100-Hz stimulation was optimal for inducing long-term potentiation (LTP). OT paired with 100-Hz stimulation that only produced short-term potentiation enhanced LTP induction in a dose-dependent manner. OT-paired LTP was blocked by both the selective OT antagonist desGly-NH(2),d(CH(2))(5)[Tyr(Me)(2),Thr(4)]-ornithine vasotocin and the N-methyl-d-aspartate (NMDA) receptor antagonist dl-2-amino-5-phosphonovaleric acid. These results indicate that OT can function as a gate to modulate the establishment of NMDA receptor-dependent LTP at the mitral-to-granule cell synapse in the AOB.

  4. Impaired long-term potentiation induction in dentate gyrus of calretinin-deficient mice

    PubMed Central

    Schurmans, Stéphane; Schiffmann, Serge N.; Gurden, Hirac; Lemaire, Martine; Lipp, Hans-Peter; Schwam, Valérie; Pochet, Roland; Imperato, Assunta; Böhme, Georg Andrees; Parmentier, Marc

    1997-01-01

    Calretinin (Cr) is a Ca2+ binding protein present in various populations of neurons distributed in the central and peripheral nervous systems. We have generated Cr-deficient (Cr−/−) mice by gene targeting and have investigated the associated phenotype. Cr−/− mice were viable, and a large number of morphological, biochemical, and behavioral parameters were found unaffected. In the normal mouse hippocampus, Cr is expressed in a widely distributed subset of GABAergic interneurons and in hilar mossy cells of the dentate gyrus. Because both types of cells are part of local pathways innervating dentate granule cells and/or pyramidal neurons, we have explored in Cr−/− mice the synaptic transmission between the perforant pathway and granule cells and at the Schaffer commissural input to CA1 pyramidal neurons. Cr−/− mice showed no alteration in basal synaptic transmission, but long-term potentiation (LTP) was impaired in the dentate gyrus. Normal LTP could be restored in the presence of the GABAA receptor antagonist bicuculline, suggesting that in Cr−/− dentate gyrus an excess of γ-aminobutyric acid (GABA) release interferes with LTP induction. Synaptic transmission and LTP were normal in CA1 area, which contains only few Cr-positive GABAergic interneurons. Cr−/− mice performed normally in spatial memory task. These results suggest that expression of Cr contributes to the control of synaptic plasticity in mouse dentate gyrus by indirectly regulating the activity of GABAergic interneurons, and that Cr−/− mice represent a useful tool to understand the role of dentate LTP in learning and memory. PMID:9294225

  5. Diabetes mellitus- and ageing-induced changes in the capacity for long-term depression and long-term potentiation inductions: toward a unified mechanism.

    PubMed

    Artola, Alain

    2013-11-05

    Long-lasting type 1 and type 2 diabetes mellitus (DM) are both associated with impaired cognitive function in humans. Animal models of DM have confirmed the detrimental effect of high blood glucose levels on learning and memory. What are the neural correlates of such impaired cognition? It is widely, although not universally, believed that long-lasting increase and decrease in synaptic strength, known as long-term potentiation (LTP) and depression (LTD), provide an important key to understanding the cellular and molecular mechanisms by which memories are formed and stored. The majority of animal studies that examined the effect of DM on LTD and LTP used the streptozotocin (STZ) rodent model of type 1 DM, with the exception of a few that used genetic models of type 2 DM. Studies in STZ-DM rodents show that cellular processes underlying synapse strengthening or weakening are not altered. Rather, the capacity for LTP induction is reduced whereas that for LTD induction is enhanced. The mechanisms underlying DM-related changes in LTD and LTP inductions are still unknown. However, that the levels of effective postsynaptic depolarization for LTD and LTP inductions are concomitantly shifted in opposite directions put constraints on them. Moreover, that DM-, metaplasticity-, stress- and ageing-related changes in LTD and LTP inductions exhibit the very same phenomenology suggests that they might involve common mechanisms. Dissecting out the mechanisms responsible for DM-related changes in the capacity for LTD and LTP inductions is helping to improve treatment of impaired cognitive function in DM patients.

  6. Long-term potentiation in hippocampal oriens interneurons: postsynaptic induction, presynaptic expression and evaluation of candidate retrograde factors.

    PubMed

    Nicholson, Elizabeth; Kullmann, Dimitri M

    2014-01-05

    Several types of hippocampal interneurons exhibit a form of long-term potentiation (LTP) that depends on Ca(2+)-permeable AMPA receptors and group I metabotropic glutamate receptors. Several sources of evidence point to a presynaptic locus of LTP maintenance. The retrograde factor that triggers the expression of LTP remains unidentified. Here, we show that trains of action potentials in putative oriens-lacunosum-moleculare interneurons of the mouse CA1 region can induce long-lasting potentiation of stimulus-evoked excitatory postsynaptic currents that mimics LTP elicited by high-frequency afferent stimulation. We further report that blockers of nitric oxide production or TRPV1 receptors failed to prevent LTP induction. The present results add to the evidence that retrograde signalling underlies N-methyl-d-aspartate (NMDA) receptor-independent LTP in oriens interneurons, mediated by an unidentified factor.

  7. Endogenous neurotrophins are required for the induction of GABAergic long-term potentiation in the neonatal rat hippocampus.

    PubMed

    Gubellini, Paolo; Ben-Ari, Yehezkel; Gaïarsa, Jean-Luc

    2005-06-15

    In the developing rat hippocampus, GABAergic synapses undergo a Ca2+-dependent long-term potentiation (LTP(GABA-A)); this form of synaptic plasticity is induced in CA3 pyramidal neurons by delivering repetitive depolarizing pulses (DPs) to the recorded neuron, and it is expressed as a long-lasting increase in the frequency and amplitude of spontaneous GABA(A) receptor-mediated postsynaptic currents. In the present study, we examined the role of endogenous tropomyosin-related kinase receptor B (TrkB) receptor ligands and associated protein tyrosine kinases (PTKs) in the induction of LTP(GABA-A). The application of Lavendustin A, a broad spectrum PTK inhibitor, blocked the induction of LTP(GABA-A), whereas Lavendustin B, its inactive form, had no effect. Moreover, k-252a and k-252b, two alkaloids that inhibit the kinase activity of the Trk receptor family, also prevented the induction of LTP(GABA-A). On hippocampal slices incubated with the soluble form of TrkB receptor IgG (TrkB-IgG), which prevents the activation of TrkB receptors by endogenous ligands, DPs failed to induce LTP(GABA-A), whereas the incubation with TrkA-IgG or TrkC-IgG had no such effect. Altogether, these data indicate that endogenous TrkB ligands and associated PTK activity are necessary for the induction of GABAergic LTP in the developing rat hippocampus.

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

    ERIC Educational Resources Information Center

    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…

  9. Proteasome Inhibition Enhances the Induction and Impairs the Maintenance of Late-Phase Long-Term Potentiation

    ERIC Educational Resources Information Center

    Dong, Chenghai; Upadhya, Sudarshan C.; Ding, Lan; Smith, Thuy K.; Hegde, Ashok N.

    2008-01-01

    Protein degradation by the ubiquitin-proteasome pathway plays important roles in synaptic plasticity, but the molecular mechanisms by which proteolysis regulates synaptic strength are not well understood. We investigated the role of the proteasome in hippocampal late-phase long-term potentiation (L-LTP), a model for enduring synaptic plasticity.…

  10. Protein Kinase M[Zeta] Is Essential for the Induction and Maintenance of Dopamine-Induced Long-Term Potentiation in Apical CA1 Dendrites

    ERIC Educational Resources Information Center

    Navakkode, Sheeja; Sajikumar, Sreedharan; Sacktor, Todd Charlton; Frey, Julietta U.

    2010-01-01

    Dopaminergic D1/D5-receptor-mediated processes are important for certain forms of memory as well as for a cellular model of memory, hippocampal long-term potentiation (LTP) in the CA1 region of the hippocampus. D1/D5-receptor function is required for the induction of the protein synthesis-dependent maintenance of CA1-LTP (L-LTP) through activation…

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

    PubMed

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

    2015-12-01

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

  12. 5-HT4-Receptors Modulate Induction of Long-Term Depression but Not Potentiation at Hippocampal Output Synapses in Acute Rat Brain Slices

    PubMed Central

    Wawra, Matthias; Fidzinski, Pawel; Heinemann, Uwe; Mody, Istvan; Behr, Joachim

    2014-01-01

    The subiculum is the principal target of CA1 pyramidal cells and mediates hippocampal output to various cortical and subcortical regions of the brain. The majority of subicular pyramidal cells are burst-spiking neurons. Previous studies indicated that high frequency stimulation in subicular burst-spiking cells causes presynaptic NMDA-receptor dependent long-term potentiation (LTP) whereas low frequency stimulation induces postsynaptic NMDA-receptor-dependent long-term depression (LTD). In the present study, we investigate the effect of 5-hydroxytryptamine type 4 (5-HT4) receptor activation and blockade on both forms of synaptic plasticity in burst-spiking cells. We demonstrate that neither activation nor block of 5-HT4 receptors modulate the induction or expression of LTP. In contrast, activation of 5-HT4 receptors facilitates expression of LTD, and block of the 5-HT4 receptor prevents induction of short-term depression and LTD. As 5-HT4 receptors are positively coupled to adenylate cyclase 1 (AC1), 5-HT4 receptors might modulate PKA activity through AC1. Since LTD is blocked in the presence of 5-HT4 receptor antagonists, our data are consistent with 5-HT4 receptor activation by ambient serotonin or intrinsically active 5-HT4 receptors. Our findings provide new insight into aminergic modulation of hippocampal output. PMID:24505387

  13. The role of dendritic action potentials and Ca2+ influx in the induction of homosynaptic long-term depression in hippocampal CA1 pyramidal neurons.

    PubMed

    Christie, B R; Magee, J C; Johnston, D

    1996-01-01

    Long-term depression (LTD) of synaptic efficacy at CA1 synapses is believed to be a Ca(2+)-dependent process. We used high-speed fluorescence imaging and patch-clamp techniques to quantify the spatial distribution of changes in intracellular Ca2+ accompanying the induction of LTD at Schaffer collateral synapses in CA1 pyramidal neurons. Low-frequency stimulation (3 Hz), which was subthreshold for action potentials, produced small changes in [Ca2+]i and failed to elicit LTD. Increasing the stimulus strength so that action potentials were generated produced both robust LTD and increases in [Ca2+]i. Back-propagating action potentials at 3 Hz in the absence of synaptic stimulation also produced increases in [Ca2+]i, but failed to induce LTD. When subthreshold synaptic stimulation was paired with back-propagating action potentials, however, large increases in [Ca2+]i were observed and robust LTD was induced. The LTD was blocked by the N-methyl-D-aspartate receptor (NMDAr) antagonist APV, and stimulus-induced increases in [Ca2+]i were reduced throughout the neuron under these conditions. The LTD was also dependent on Ca2+ influx via voltage-gated Ca2+ channels (VGCCs), because LTD was severely attenuated or blocked by both nimodipine and Ni2+. These findings suggest that back-propagating action potentials can exert a powerful control over the induction of LTD and that both VGCCs and NMDArs are involved in the induction of this form of plasticity.

  14. Natural drug extracts for a nutritive-tonic drink, promotes the induction of long-term potentiation in rat hippocampal dentate gyrus in vivo.

    PubMed

    Sakata, Yasuko; Ishige, Kumiko; Ohtakara, Tomohiro; Ito, Yoshihisa

    2006-07-01

    We have shown previously that oral administration of a nutritive-tonic drink (NTD) improves scopolamine-induced memory impairment in the passive avoidance task and Morris water-maze in mice and that this action is attributable to the natural drug extracts, rather than synthetic drugs such as taurine and caffeine, in the NTD. In order to investigate the mechanism underlying the antiamnesic effects of the natural drug extracts, the effects of the extracts on the induction of long-term potentiation (LTP) was investigated in the dentate gyrus (DG) of normal and scopolamine-treated rats. Oral administration of natural drug extracts enhanced the induction of population spike amplitude induced by weak tetanic stimulation (30 pulses at 60 Hz). Scopolamine (0.3 mg/kg, i.p.) completely inhibited the induction of LTP induced by both weak and strong tetanic stimulation (100 pulses at 100 Hz). Natural drug extracts enhanced partially but significantly the induction of LTP by strong tetanus, but had a very weak effect on that induced by weak tetanus. These results suggest that LTP induced by strong tetanus is sensitive to natural drug extracts, and that the antiamnesic effect of the NTD is at least partly attributable to the LTP-improving effect of the natural drug extracts in the DG.

  15. Clonidine suppresses the induction of long-term potentiation by inhibiting HCN channels at the Schaffer collateral-CA1 synapse in anesthetized adult rats.

    PubMed

    Li, Chang-Jun; Zhou, Mei; Li, Hui-Ge; Lv, Qing; Xu, Xu-Lin; Guo, Lian-Jun

    2013-11-01

    Activation of alpha2-adrenoceptors inhibits long-term potentiation and long-term depression in many brain regions. However, effectiveness and mechanism of alpha2-adrenoceptors for synaptic plasticity at the Schaffer collateral-CA1 synapses in rat in vivo is unclear. In the present study, we investigated the effects of alpha2-adrenoceptors agonist clonidine on high-frequency stimulation (HFS)-induced long-term potentiation (LTP) and paired-pulse facilitation (PPF) at the Schaffer collateral-CA1 synapse of rat hippocampus in vivo. Clonidine (0.05, 0.1 mg/kg, ip) inhibited synaptic plasticity in a dose-dependent manner, accompanying with the decreasing of aortic pressure and heart rate (HR) in anesthetized rats. Clonidine (1.25, 2.5 μg/kg, icv, 10 min before HFS) also dose-dependently inhibited synaptic plasticity, which had no remarkable effect on HR and aortic pressure. But, 20 min after HFS, administration of clonidine (2.5 μg/kg) had no effect on LTP. The inhibitory effect of clonidine (2.5 μg/kg) on LTP was completely reversed by yohimbine (18 μg/kg, icv) and ZD7288 (5 μg/kg, icv). Moreover, the inhibition was accompanied by a significant increase of the normalized PPF ratio. Furthermore, clonidine at 1 and 10 μM significantly decreased glutamate (Glu) content in the culture supernatants of hippocampal neurons, and yohimbine at 1 and 10 μM had no effect on Glu release, while it could reverse the inhibition of clonidine (1 and 10 μM) on Glu release. In conclusion, clonidine can suppress the induction of LTP at the Schaffer collateral-CA1 synapse, and the possible mechanism is that activation of presynaptic alpha2-adrenoceptors reduces the Glu release by inhibiting HCN channels.

  16. Nicotine facilitates long-term potentiation induction in oriens-lacunosum moleculare cells via Ca2+ entry through non-alpha7 nicotinic acetylcholine receptors.

    PubMed

    Jia, Yousheng; Yamazaki, Yoshihiko; Nakauchi, Sakura; Ito, Ken-Ichi; Sumikawa, Katumi

    2010-02-01

    Hippocampal inhibitory interneurons have a central role in the control of network activity, and excitatory synapses that they receive express Hebbian and anti-Hebbian long-term potentiation (LTP). Because many interneurons in the hippocampus express nicotinic acetylcholine receptors (nAChRs), we explored whether exposure to nicotine promotes LTP induction in these interneurons. We focussed on a subset of interneurons in the stratum oriens/alveus that were continuously activated in the presence of nicotine due to the expression of non-desensitizing non-alpha7 nAChRs. We found that, in addition to alpha2 subunit mRNAs, these interneurons were consistently positive for somatostatin and neuropeptide Y mRNAs, and showed morphological characteristics of oriens-lacunosum moleculare cells. Activation of non-alpha7 nAChRs increased intracellular Ca(2+) levels at least in part via Ca(2+) entry through their channels. Presynaptic tetanic stimulation induced N-methyl-D-aspartate receptor-independent LTP in voltage-clamped interneurons at -70 mV when in the presence, but not absence, of nicotine. Intracellular application of a Ca(2+) chelator blocked LTP induction, suggesting the requirement of Ca(2+) signal for LTP induction. The induction of LTP was still observed in the presence of ryanodine, which inhibits Ca(2+) -induced Ca(2+) release from ryanodine-sensitive intracellular stores, and the L-type Ca(2+) channel blocker nifedipine. These results suggest that Ca(2+) entry through non-alpha7 nAChR channels is critical for LTP induction. Thus, nicotine affects hippocampal network activity by promoting LTP induction in oriens-lacunosum moleculare cells via continuous activation of non-alpha7 nAChRs.

  17. Induction of long-term potentiation and depression is reflected by corresponding changes in secretion of endogenous brain-derived neurotrophic factor

    PubMed Central

    Aicardi, Giorgio; Argilli, Emanuela; Cappello, Silvia; Santi, Spartaco; Riccio, Massimo; Thoenen, Hans; Canossa, Marco

    2004-01-01

    Neurotrophins play an important role in modulating activity-dependent neuronal plasticity. In particular, threshold levels of brain-derived neurotrophic factor (BDNF) are required to induce long-term potentiation (LTP) in acute hippocampal slices. Conversely, the administration of exogenous BDNF prevents the induction of long-term depression (LTD) in the visual cortex. A long-standing missing link in the analysis of this modulatory role of BDNF was the determination of the time-course of endogenous BDNF secretion in the same organotypic preparation in which LTP and LTD are elicited. Here, we fulfilled this requirement in slices of perirhinal cortex. Classical theta-burst stimulation patterns evoking LTP lasting >180 min elicited a large increase in BDNF secretion that persisted 5-12 min beyond the stimulation period. Weaker theta-burst stimulation patterns leading only to the initial phase of LTP (≈35 min) were accompanied by a smaller increase in BDNF secretion lasting <1 min. Sequestration of BDNF by TrkB-IgG receptor bodies prevented LTP. Low-frequency stimulations leading to LTD were accompanied by reductions in BDNF secretion that never lasted beyond the duration of the stimulation. PMID:15505222

  18. Induction of long-term potentiation in single nociceptive dorsal horn neurons is blocked by the CaMKII inhibitor AIP.

    PubMed

    Pedersen, Linda Margareth; Lien, Guro Flor; Bollerud, Ingunn; Gjerstad, Johannes

    2005-04-11

    Neuronal events leading to development of long-term potentiation (LTP) in the nociceptive pathways may be a cellular mechanism underlying central hyperalgesia. Here, we examine whether induction of LTP in nociceptive dorsal horn neurons at depths of 80-500 microm from the cord surface can be affected by spinal application of the Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) inhibitor AIP. Extracellular recordings from single neurons in intact urethane anesthetized Sprague-Dawley rats were performed, and the neuronal A-fiber and C-fiber responses after sciatic nerve test pulses were defined according to latencies. A clear LTP of the nociceptive transmission following sciatic nerve high-frequency stimulation (HFS) was observed in single neurons in laminae I-IV of the dorsal horn. The increase in the C-fiber response after HFS was blocked in the presence of 2.0 mM AIP (P < 0.05 HFS group versus AIP + HFS group 2 h after conditioning). However, the C-fiber response was not affected by 2.0 mM AIP alone or by vehicle. Thus, our data show that the neuronal process leading to the induction of LTP in the dorsal horn induced by HFS is clearly inhibited by the specific CaMKII inhibitor AIP. It is concluded that CaMKII may be important for the induction of LTP in single nociceptive dorsal horn neurons.

  19. Deletion of Kv4.2 gene eliminates dendritic A-type K+ current and enhances induction of long-term potentiation in hippocampal CA1 pyramidal neurons.

    PubMed

    Chen, Xixi; Yuan, Li-Lian; Zhao, Cuiping; Birnbaum, Shari G; Frick, Andreas; Jung, Wonil E; Schwarz, Thomas L; Sweatt, J David; Johnston, Daniel

    2006-11-22

    Dendritic, backpropagating action potentials (bAPs) facilitate the induction of Hebbian long-term potentiation (LTP). Although bAPs in distal dendrites of hippocampal CA1 pyramidal neurons are attenuated when propagating from the soma, their amplitude can be increased greatly via downregulation of dendritic A-type K+ currents. The channels that underlie these currents thus may represent a key regulatory component of the signaling pathways that lead to synaptic plasticity. We directly tested this hypothesis by using Kv4.2 knock-out mice. Deletion of the Kv4.2 gene and a loss of Kv4.2 protein resulted in a specific and near-complete elimination of A-type K+ currents from the apical dendrites of CA1 pyramidal neurons. The absence of dendritic Kv4.2-encoded A-type K+ currents led to an increase of bAP amplitude and an increase of concurrent Ca2+ influx. Furthermore, CA1 pyramidal neurons lacking dendritic A-type K+ currents from Kv4.2 knock-out mice exhibited a lower threshold than those of wild-type littermates for LTP induction with the use of a theta burst pairing protocol. LTP triggered with the use of a saturating protocol, on the other hand, remained indistinguishable between Kv4.2 knock-out and wild-type neurons. Our results support the hypothesis that dendritic A-type K+ channels, composed of Kv4.2 subunits, regulate action potential backpropagation and the induction of specific forms of synaptic plasticity.

  20. Long-term depression of excitatory synaptic transmission and its relationship to long-term potentiation.

    PubMed

    Artola, A; Singer, W

    1993-11-01

    In many brain areas, including the cerebellar cortex, neocortex, hippocampus, striatum and nucleus accumbens, brief activation of an excitatory pathway can produce long-term depression (LTD) of synaptic transmission. In most preparations, induction of LTD has been shown to require a minimum level of postsynaptic depolarization and a rise in the intracellular Ca2+ concentration [Ca2+]i in the postsynaptic neurone. Thus, induction conditions resemble those described for the initiation of associative long-term potentiation (LTP). However, data from structures susceptible to both LTD and LTP suggest that a stronger depolarization and a greater increase in [Ca2+]i are required to induce LTP than to initiate LTD. The source of Ca2+ appears to be less critical for the differential induction of LTP and LTD than the amplitude of the Ca2+ surge, since the activation of voltage- and ligand-gated Ca2+ conductances as well as the release from intracellular stores have all been shown to contribute to both LTD and LTP induction. LTD is induceable even at inactive synapses if [Ca2+]i is raised to the appropriate level by antidromic or heterosynaptic activation, or by raising the extracellular Ca2+ concentration [Ca2+]o. These conditions suggest a rule (called here the ABS rule) for activity-dependent synaptic modifications that differs from the classical Hebb rule and that can account for both homosynaptic LTD and LTP as well as for heterosynaptic competition and associativity.

  1. REM sleep deprivation-induced deficits in the latency-to-peak induction and maintenance of long-term potentiation within the CA1 region of the hippocampus.

    PubMed

    Davis, Christopher J; Harding, Joseph W; Wright, John W

    2003-05-30

    Sleep loss adversely affects certain types of cognitive processing, particularly associative memory. Given that long-term potentiation (LTP) represents a putative cellular basis of learning and memory consolidation, the influence of sleep deprivation on LTP was examined. Rats were REM sleep deprived for 24, 48, or 72 h using the inverted flowerpot method in temperature-regulated chambers. Hippocampal slices taken from sleep-deprived rats were compared with home cage and pedestal control animals at 5, 15 and 60 min post-tetanization. The results indicated that at 5 min post-tetanization there were no differences in field potentials in any of the sleep-deprived or control groups, suggesting comparable levels of induction. However, analysis of latency-to-peak slope indicated that members of the 48 and 72 h sleep-deprived groups required approximately twice as long to achieve maximum slope as the 24 h group, home cage or 24, 48, 72 h pedestal controls (means 8.17, 7.50, 2.67, 4.67 and 3.17 min, respectively). At 15 min post-tetanization there were no group differences, however at 60 min post-tetanization the slopes of the field excitatory postsynaptic potentials were significantly diminished for the 24, 48 and 72 h sleep-deprived groups (means 30.44, -1.89, 1.47, respectively) as compared with home cage and pedestal controls (means 59.54, 58.42, respectively). This delay in maximal induction, and the degradation of the maintenance phase of LTP, may represent sleep deprivation-induced impairment of the underlying neurochemical mechanisms normally responsible for memory acquisition.

  2. An interchangeable role for kainate and metabotropic glutamate receptors in the induction of rat hippocampal mossy fiber long-term potentiation in vivo

    PubMed Central

    Wallis, James L; Irvine, Mark W; Jane, David E; Lodge, David; Collingridge, Graham L; Bortolotto, Zuner A

    2015-01-01

    The roles of both kainate receptors (KARs) and metabotropic glutamate receptors (mGluRs) in mossy fiber long-term potentiation (MF-LTP) have been extensively studied in hippocampal brain slices, but the findings are controversial. In this study, we have addressed the roles of both mGluRs and KARs in MF-LTP in anesthetized rats. We found that MF-LTP could be induced in the presence of either GluK1-selective KAR antagonists or group I mGluR antagonists. However, LTP was inhibited when the group I mGluRs and the GluK1-KARs were simultaneously inhibited. Either mGlu1 or mGlu5 receptor activation is sufficient to induce this form of LTP as selective inhibition of either subtype alone, together with the inhibition of KARs, did not inhibit MF-LTP. These data suggest that mGlu1 receptors, mGlu5 receptors, and GluK1-KARs are all engaged during high-frequency stimulation, and that the activation of any one of these receptors alone is sufficient for the induction of MF-LTP in vivo. © 2015 The Authors Hippocampus Published by Wiley Periodicals, Inc. PMID:25821051

  3. Brain-derived neurotrophic factor-mediated retrograde signaling required for the induction of long-term potentiation at inhibitory synapses of visual cortical pyramidal neurons.

    PubMed

    Inagaki, Tsuyoshi; Begum, Tahamina; Reza, Faruque; Horibe, Shoko; Inaba, Mie; Yoshimura, Yumiko; Komatsu, Yukio

    2008-06-01

    High-frequency stimulation (HFS) induces long-term potentiation (LTP) at inhibitory synapses of layer 5 pyramidal neurons in developing rat visual cortex. This LTP requires postsynaptic Ca2+ rise for induction, while the maintenance mechanism is present at the presynaptic site, suggesting presynaptic LTP expression and the necessity of retrograde signaling. We investigated whether the supposed signal is mediated by brain-derived neurotrophic factor (BDNF), which is expressed in pyramidal neurons but not inhibitory interneurons. LTP did not occur when HFS was applied in the presence of the Trk receptor tyrosine kinase inhibitor K252a in the perfusion medium. HFS produced LTP when bath application of K252a was started after HFS or when K252a was loaded into postsynaptic cells. LTP did not occur in the presence of TrkB-IgG scavenging BDNF or function-blocking anti-BDNF antibody in the medium. In cells loaded with the Ca2+ chelator BAPTA, the addition of BDNF to the medium enabled HFS to induce LTP without affecting baseline synaptic transmission. These results suggest that BDNF released from postsynaptic cells activates presynaptic TrkB, leading to LTP. Because BDNF, expressed activity dependently, regulates the maturation of cortical inhibition, inhibitory LTP may contribute to this developmental process, and hence experience-dependent functional maturation of visual cortex.

  4. Protein kinase Mζ is essential for the induction and maintenance of dopamine-induced long-term potentiation in apical CA1 dendrites

    PubMed Central

    Navakkode, Sheeja; Sajikumar, Sreedharan; Sacktor, Todd Charlton; Frey, Julietta U.

    2010-01-01

    Dopaminergic D1/D5-receptor-mediated processes are important for certain forms of memory as well as for a cellular model of memory, hippocampal long-term potentiation (LTP) in the CA1 region of the hippocampus. D1/D5-receptor function is required for the induction of the protein synthesis-dependent maintenance of CA1-LTP (L-LTP) through activation of the cAMP/PKA-pathway. In earlier studies we had reported a synergistic interaction of D1/D5-receptor function and N-methyl-D-aspartate (NMDA)-receptors for L-LTP. Furthermore, we have found the requirement of the atypical protein kinase C isoform, protein kinase Mζ (PKMζ) for conventional electrically induced L-LTP, in which PKMζ has been identified as a LTP-specific plasticity-related protein (PRP) in apical CA1-dendrites. Here, we investigated whether the dopaminergic pathway activates PKMζ. We found that application of dopamine (DA) evokes a protein synthesis-dependent LTP that requires synergistic NMDA-receptor activation and protein synthesis in apical CA1-dendrites. We identified PKMζ as a DA-induced PRP, which exerted its action at activated synaptic inputs by processes of synaptic tagging. PMID:21084457

  5. Long-term potentiation: peeling the onion.

    PubMed

    Nicoll, Roger A; Roche, Katherine W

    2013-11-01

    Since the discovery of long-term potentiation (LTP), thousands of papers have been published on this phenomenon. With this massive amount of information, it is often difficult, especially for someone not directly involved in the field, not to be overwhelmed. The goal of this review is to peel away as many layers as possible, and probe the core properties of LTP. We would argue that the many dozens of proteins that have been implicated in the phenomenon are not essential, but rather modulate, often in indirect ways, the threshold and/or magnitude of LTP. What is required is NMDA receptor activation followed by CaMKII activation. The consequence of CaMKII activation is the rapid recruitment of AMPA receptors to the synapse. This recruitment is independent of AMPA receptor subunit type, but absolutely requires an adequate pool of surface receptors. An important unresolved issue is how exactly CaMKII activation leads to modifications in the PSD to allow rapid enrichment. This article is part of the Special Issue entitled 'Glutamate Receptor-Dependent Synaptic Plasticity'.

  6. Changes in Synaptic Transmission and Long-term Potentiation Induction as a Possible Mechanism for Learning Disability in an Animal Model of Multiple Sclerosis

    PubMed Central

    2016-01-01

    Purpose: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. It has been shown that memory deficits is common in patients with MS. Recent studies using experimental autoimmune encephalomyelitis (EAE) as an animal model of MS have shown that indicated that EAE causes hippocampal-dependent impairment in learning and memory. Thus far, there have been no in vivo electrophysiological reports describing synaptic transmission in EAE animals. The aim of the present work is to evaluate the synaptic changes in the CA1 region of the hippocampus of EAE rats. Methods: To evaluate changes in synaptic transmission in the CA1 region of the hippocampus of EAE rats, field excitatory postsynaptic potentials (fEPSPs) from the stratum radiatum of CA1 neurons, were recorded following Schaffer collateral stimulation. Results: The results showed that EAE causes deficits in synaptic transmission and long-term potentiation (LTP) in the hippocampus. In addition, paired-pulse index with a 120 msec interstimulus interval was decreased in the EAE group. These findings indicate that EAE might induce suppression in synaptic transmission and LTP by increasing the inhibitory effect of GABAB receptors on the glutamate-mediated EPSP. Conclusions: In conclusion, influence of inflammation-triggered mechanisms on synaptic transmission may explain the negative effect of EAE on learning abilities in rats. PMID:27032554

  7. Gene expression associated with in vivo induction of early phase-long-term potentiation (LTP) in the hippocampal mossy fiber-Cornus Ammonis (CA)3 pathway.

    PubMed

    Thompson, K J; Orfila, J E; Achanta, P; Martinez, J L

    2003-12-01

    Affymetrix microarray technology was used to characterize whole-hippocampus gene expression associated with in vivo N-methyl-D-aspartate (NMDA)-R-independent long-term potentiation (LTP) in the mossy fiber (MF)-Cornus Ammonis (CA)3 pathway of adult male F344 rats. Acute MF responses were evoked by stimulation of the MF bundle and recorded in stratum lucidum of CA3. Following recording of baseline responses at 0.05 Hz, animals received either CPP (NMDA-R antagonist, 10 mg/kg) or naloxone (opioid-R antagonist, 10 mg/kg). LTP was induced by two 100 Hz 1-sec trains at the intensity sufficient to evoke 50% of the maximal response. Responses were collected for an additional hour. In controls, MF responses were collected at 0.05 Hz for 1 hr, but 100 Hz trains were not delivered. Hippocampi were harvested prior to total RNA isolation. Fragmented cRNA was hybridized to a rat U34 neurobiology array. F344 rats exhibited characteristic LTP in the presence of CPP and LTP blockade in the presence of naloxone. As a result, genes associated with both NMDA-independent LTP and naloxone-induced blockade were identified. These include genes involved in transmitter transport, intracellular messengers, growth factors and ion channels. Up-regulated include NMDA-R2D, neuropeptide Y (NPY), proenkephalin, BDNF and NGFR. Down-regulated genes include IGF-1 and GABA-B.

  8. Selective induction of metabotropic glutamate receptor 1- and metabotropic glutamate receptor 5-dependent chemical long-term potentiation at oriens/alveus interneuron synapses of mouse hippocampus.

    PubMed

    Le Vasseur, M; Ran, I; Lacaille, J-C

    2008-01-02

    Synaptic plasticity in inhibitory interneurons is essential to maintain a proper equilibrium between excitation and inhibition in hippocampal network. Recent studies showed that theta-burst-induced long-term potentiation (LTP) at excitatory synapses of oriens/alveus (O/A) interneurons in CA1 hippocampal region required the activation of metabotropic glutamate receptor (mGluR) 1. However these interneurons also express mGluR5 and the contribution of this receptor subtype in interneuron synaptic plasticity remains unexplored. We combined pharmacological and transgenic approaches to examine the relative contribution of mGluR1/5 in LTP at excitatory synapses on O/A interneurons. Bath-application of the selective mGluR1/5 agonist (s)-3,5-dihydroxyphenylglycine (DHPG) induced LTP of compound excitatory postsynaptic potentials. DHPG-induced LTP was not prevented by application of either mGluR1 or mGluR5 antagonists, was still present in mGluR1 knockout mice, but was blocked by co-application of both antagonists. These results indicate that LTP can be induced at O/A interneuron synapses by either mGluR1 or mGluR5 activation. As previously reported for mGluR1-dependent LTP, the mGluR5-dependent LTP was independent of N-methyl-d-aspartate receptors. Pairing DHPG application with postsynaptic depolarization induced mGluR1- and mGluR5-dependent LTP of minimally-evoked excitatory postsynaptic currents, which were composed of calcium-permeable AMPA receptor and presynaptically modulated by group II mGluRs, hence confirming that both forms of LTP occurred directly at interneuron excitatory synapses. These findings uncover a new mGluR5-dependent form of LTP at O/A interneuron synapses and indicate that activation of mGluR1 or mGluR5 is sufficient to induce LTP at these synapses. Thus, a rich repertoire of adaptive changes may take place at these interneuron synapses to regulate hippocampal feedback inhibition.

  9. Neurophysiological analysis of long-term potentiation in mammalian brain.

    PubMed

    Voronin, L; Byzov, A; Kleschevnikov, A; Kozhemyakin, M; Kuhnt, U; Volgushev, M

    1995-01-23

    Long-term potentiation (LTP) is a persistent increase in postsynaptic response following a high-frequency presynaptic activation. Characteristic LTP features, including input specificity and associativity, make it a popular model to study memory mechanisms. Mechanisms of LTP induction and maintenance are briefly reviewed. Increased intracellular Ca2+ concentration is shown to be critical for LTP induction. This increase is believed to be based on Ca2+ influx secondary to activation of N-methyl-D-aspartate (NMDA) subtype of glutamate receptors. Existence of other sources of Ca2+ increase and other critical factors is now becoming evident. They include voltage-dependent Ca2+ channels, Ca2+ intracellular stores, metabotropic glutamate receptors, 'modulatory' transmitters. An example of an involvement of voltage-dependent Ca2+ channels is potentiation induced by intracellular depolarizing pulses. LTP can be divided into decremental earlier (E-LTP) and non-decremental late (L-LTP) phases which explains some inconsistencies in studies of LTP mechanisms. E-LTP is suggested to be based on a transient increase in presynaptic release probabilities. A hypothesis is considered which explains L-LTP by suggesting that Ca2+ activates structural changes leading to an increase in the synaptic gap resistance. This enhances positive synaptic electrical feedback and augments release probability. The hypothesis predicts specific morphological changes, synchronous transmitter release of two or several quanta in some central synapses and the amplification of such synchronization following LTP induction. Data are discussed which maintain these predictions.

  10. Pediatric Facial Fractures and Potential Long-Term Growth Disturbances

    PubMed Central

    Wheeler, Jonathan; Phillips, John

    2011-01-01

    Fractures of the pediatric craniofacial skeleton can be challenging to manage. The initial injury and subsequent treatment can cause long-term growth disturbances yielding problematic secondary deformities. This review considers the normal growth of the craniofacial skeleton and typical facial fracture presentations in children and discusses the potential long-term sequelae from these injuries and their management. PMID:22379506

  11. Activation of Metabotropic Glutamate Receptor 7 Is Required for Induction of Long-Term Potentiation at SC-CA1 Synapses in the Hippocampus

    PubMed Central

    Klar, Rebecca; Walker, Adam G.; Ghose, Dipanwita; Grueter, Brad A.; Engers, Darren W.; Hopkins, Corey R.; Lindsley, Craig W.; Xiang, Zixiu

    2015-01-01

    Of the eight metabotropic glutamate (mGlu) receptor subtypes, only mGlu7 is expressed presynaptically at the Schaffer collateral (SC)-CA1 synapse in the hippocampus in adult animals. Coupled with the inhibitory effects of Group III mGlu receptor agonists on transmission at this synapse, mGlu7 is thought to be the predominant autoreceptor responsible for regulating glutamate release at SC terminals. However, the lack of mGlu7-selective pharmacological tools has hampered direct testing of this hypothesis. We used a novel, selective mGlu7-negative allosteric modulator (NAM), ADX71743, and a newly described Group III mGlu receptor agonist, LSP4-2022, to elucidate the role of mGlu7 in modulating transmission in hippocampal area CA1 in adult C57BL/6J male mice. Interestingly, although mGlu7 agonists inhibit SC-CA1 EPSPs, we found no evidence for activation of mGlu7 by stimulation of SC-CA1 afferents. However, LSP4-2022 also reduced evoked monosynaptic IPSCs in CA1 pyramidal cells and, in contrast to its effect on SC-CA1 EPSPs, ADX71743 reversed the ability of high-frequency stimulation of SC afferents to reduce IPSC amplitudes. Furthermore, blockade of mGlu7 prevented induction of LTP at the SC-CA1 synapse and activation of mGlu7 potentiated submaximal LTP. Together, these data suggest that mGlu7 serves as a heteroreceptor at inhibitory synapses in area CA1 and that the predominant effect of activation of mGlu7 by stimulation of glutamatergic afferents is disinhibition, rather than reduced excitatory transmission. Furthermore, this mGlu7-mediated disinhibition is required for induction of LTP at the SC-CA1 synapse, suggesting that mGlu7 could serve as a novel therapeutic target for treatment of cognitive disorders. PMID:25972184

  12. Activation of Metabotropic Glutamate Receptor 7 Is Required for Induction of Long-Term Potentiation at SC-CA1 Synapses in the Hippocampus.

    PubMed

    Klar, Rebecca; Walker, Adam G; Ghose, Dipanwita; Grueter, Brad A; Engers, Darren W; Hopkins, Corey R; Lindsley, Craig W; Xiang, Zixiu; Conn, P Jeffrey; Niswender, Colleen M

    2015-05-13

    Of the eight metabotropic glutamate (mGlu) receptor subtypes, only mGlu7 is expressed presynaptically at the Schaffer collateral (SC)-CA1 synapse in the hippocampus in adult animals. Coupled with the inhibitory effects of Group III mGlu receptor agonists on transmission at this synapse, mGlu7 is thought to be the predominant autoreceptor responsible for regulating glutamate release at SC terminals. However, the lack of mGlu7-selective pharmacological tools has hampered direct testing of this hypothesis. We used a novel, selective mGlu7-negative allosteric modulator (NAM), ADX71743, and a newly described Group III mGlu receptor agonist, LSP4-2022, to elucidate the role of mGlu7 in modulating transmission in hippocampal area CA1 in adult C57BL/6J male mice. Interestingly, although mGlu7 agonists inhibit SC-CA1 EPSPs, we found no evidence for activation of mGlu7 by stimulation of SC-CA1 afferents. However, LSP4-2022 also reduced evoked monosynaptic IPSCs in CA1 pyramidal cells and, in contrast to its effect on SC-CA1 EPSPs, ADX71743 reversed the ability of high-frequency stimulation of SC afferents to reduce IPSC amplitudes. Furthermore, blockade of mGlu7 prevented induction of LTP at the SC-CA1 synapse and activation of mGlu7 potentiated submaximal LTP. Together, these data suggest that mGlu7 serves as a heteroreceptor at inhibitory synapses in area CA1 and that the predominant effect of activation of mGlu7 by stimulation of glutamatergic afferents is disinhibition, rather than reduced excitatory transmission. Furthermore, this mGlu7-mediated disinhibition is required for induction of LTP at the SC-CA1 synapse, suggesting that mGlu7 could serve as a novel therapeutic target for treatment of cognitive disorders.

  13. 17β estradiol recruits GluN2B-containing NMDARs and ERK during induction of long-term potentiation at temporoammonic-CA1 synapses.

    PubMed

    Smith, Caroline C; Smith, Lindsey A; Bredemann, Teruko M; McMahon, Lori L

    2016-01-01

    When circulating 17β estradiol (E2) is elevated to proestrous levels, hippocampus-dependent learning and memory is enhanced in female rodents, nonhuman primates, and women due to heightened synaptic function at hippocampal synapses. We previously reported that proestrous-like levels of E2 administered to young adult ovariectomized (OVX) female rats increases the magnitude of LTP at CA3 Schaffer collateral (SC)-CA1 synapses only when dendritic spine density, the NMDAR/AMPAR ratio, and current mediated by GluN2B-containing NMDA receptors (NMDARs) are simultaneously increased. We also reported that this increase in GluN2B-mediated NMDAR current in area CA1 is causally related to the E2-induced increase in novel object recognition, tying together heightened synaptic function with improved learning and memory. In addition to SC inputs, innervation from the entorhinal cortex in the temporoammonic (TA) pathway onto CA1 distal dendrites in stratum lacunosum-moleculare is critical for spatial memory formation and retrieval. It is not known whether E2 modulates TA-CA1 synapses similarly to SC-CA1 synapses. Here, we report that 24 hours post-E2 injection, dendritic spine density on CA1 pyramidal cell distal dendrites and current mediated by GluN2B-containing NMDARs at TA-CA1 synapses is increased, similarly to our previous findings at SC-CA1 synapses. However, in contrast to SC-CA1 synapses, AMPAR transmission at TA-CA1 synapses is significantly increased, and there is no effect on the LTP magnitude. Pharmacological blockade of GluN2B-containing NMDARs or ERK activation, which occurs downstream of synaptic but not extrasynaptic GluN2B-containing NMDARs, attenuates the LTP magnitude only in slices from E2-treated rats. These data show that E2 recruits a causal role for GluN2B-containing NMDARs and ERK signaling in the induction of LTP, cellular mechanisms not required for LTP induction at TA-CA1 synapses in vehicle-treated OVX female rats.

  14. Nuclear Translocation of Jacob in Hippocampal Neurons after Stimuli Inducing Long-Term Potentiation but Not Long-Term Depression

    PubMed Central

    Behnisch, Thomas; YuanXiang, PingAn; Bethge, Philipp; Parvez, Suhel; Chen, Ying; Yu, Jin; Karpova, Anna; Frey, Julietta U.; Mikhaylova, Marina; Kreutz, Michael R.

    2011-01-01

    Background In recent years a number of potential synapto-nuclear protein messengers have been characterized that are thought to be involved in plasticity-related gene expression, and that have the capacity of importin- mediated and activity-dependent nuclear import. However, there is a surprising paucity of data showing the nuclear import of such proteins in cellular models of learning and memory. Only recently it was found that the transcription factor cyclic AMP response element binding protein 2 (CREB2) transits to the nucleus during long-term depression (LTD), but not during long-term potentiation (LTP) of synaptic transmission in hippocampal primary neurons. Jacob is another messenger that couples NMDA-receptor-activity to nuclear gene expression. We therefore aimed to study whether Jacob accumulates in the nucleus in physiological relevant models of activity-dependent synaptic plasticity. Methodology/Principal Findings We have analyzed the dynamics of Jacob's nuclear import following induction of NMDA-receptor dependent LTP or LTD at Schaffer collateral-CA1 synapses in rat hippocampal slices. Using time-lapse imaging of neurons expressing a Jacob-Green-Fluorescent-Protein we found that Jacob rapidly translocates from dendrites to the nucleus already during the tetanization period of LTP, but not after induction of LTD. Immunocytochemical stainings confirmed the nuclear accumulation of endogenous Jacob in comparison to apical dendrites after induction of LTP but not LTD. Complementary findings were obtained after induction of NMDA-receptor dependent chemical LTP and LTD in hippocampal primary neurons. However, in accordance with previous studies, high concentrations of NMDA and glycine as well as specific activation of extrasynaptic NMDA-receptors resembling pathological conditions induce an even more profound increase of nuclear Jacob levels. Conclusions/Significance Taken together, these findings suggest that the two major forms of NMDA-receptor dependent

  15. A Brief History of Long-Term Potentiation.

    PubMed

    Nicoll, Roger A

    2017-01-18

    Since the discovery of long-term potentiation (LTP) in 1973, thousands of papers have been published on this intriguing phenomenon, which provides a compelling cellular model for learning and memory. Although LTP has suffered considerable growing pains over the years, LTP has finally come of age. Here the rich history of LTP is reviewed. These are exciting times and the pace of discovery is remarkable.

  16. Long-term potentiation, cooperativity and Hebb's cell assemblies: a personal history.

    PubMed

    McNaughton, Bruce L

    2003-04-29

    The early history of the experimental work leading to the discovery that long-term potentiation (LTP) embodies Hebb's principle of association is described. In addition, the fallacy underlying the sometimes presumed distinction between 'cooperativity' and 'associativity' in the induction of LTP is pointed out.

  17. Modeling maintenance of long-term potentiation in clustered synapses: long-term memory without bistability.

    PubMed

    Smolen, Paul

    2015-01-01

    Memories are stored, at least partly, as patterns of strong synapses. Given molecular turnover, how can synapses maintain strong for the years that memories can persist? Some models postulate that biochemical bistability maintains strong synapses. However, bistability should give a bimodal distribution of synaptic strength or weight, whereas current data show unimodal distributions for weights and for a correlated variable, dendritic spine volume. Thus it is important for models to simulate both unimodal distributions and long-term memory persistence. Here a model is developed that connects ongoing, competing processes of synaptic growth and weakening to stochastic processes of receptor insertion and removal in dendritic spines. The model simulates long-term (>1 yr) persistence of groups of strong synapses. A unimodal weight distribution results. For stability of this distribution it proved essential to incorporate resource competition between synapses organized into small clusters. With competition, these clusters are stable for years. These simulations concur with recent data to support the "clustered plasticity hypothesis" which suggests clusters, rather than single synaptic contacts, may be a fundamental unit for storage of long-term memory. The model makes empirical predictions and may provide a framework to investigate mechanisms maintaining the balance between synaptic plasticity and stability of memory.

  18. Modeling Maintenance of Long-Term Potentiation in Clustered Synapses: Long-Term Memory without Bistability

    PubMed Central

    Smolen, Paul

    2015-01-01

    Memories are stored, at least partly, as patterns of strong synapses. Given molecular turnover, how can synapses maintain strong for the years that memories can persist? Some models postulate that biochemical bistability maintains strong synapses. However, bistability should give a bimodal distribution of synaptic strength or weight, whereas current data show unimodal distributions for weights and for a correlated variable, dendritic spine volume. Thus it is important for models to simulate both unimodal distributions and long-term memory persistence. Here a model is developed that connects ongoing, competing processes of synaptic growth and weakening to stochastic processes of receptor insertion and removal in dendritic spines. The model simulates long-term (>1 yr) persistence of groups of strong synapses. A unimodal weight distribution results. For stability of this distribution it proved essential to incorporate resource competition between synapses organized into small clusters. With competition, these clusters are stable for years. These simulations concur with recent data to support the “clustered plasticity hypothesis” which suggests clusters, rather than single synaptic contacts, may be a fundamental unit for storage of long-term memory. The model makes empirical predictions and may provide a framework to investigate mechanisms maintaining the balance between synaptic plasticity and stability of memory. PMID:25945261

  19. Inhibition promotes long-term potentiation at cerebellar excitatory synapses

    PubMed Central

    Binda, F.; Dorgans, K.; Reibel, S.; Sakimura, K.; Kano, M.; Poulain, B.; Isope, P.

    2016-01-01

    The ability of the cerebellar cortex to learn from experience ensures the accuracy of movements and reflex adaptation, processes which require long-term plasticity at granule cell (GC) to Purkinje neuron (PN) excitatory synapses. PNs also receive GABAergic inhibitory inputs via GCs activation of interneurons; despite the involvement of inhibition in motor learning, its role in long-term plasticity is poorly characterized. Here we reveal a functional coupling between ionotropic GABAA receptors and low threshold CaV3 calcium channels in PNs that sustains calcium influx and promotes long-term potentiation (LTP) at GC to PN synapses. High frequency stimulation induces LTP at GC to PN synapses and CaV3-mediated calcium influx provided that inhibition is intact; LTP is mGluR1, intracellular calcium store and CaV3 dependent. LTP is impaired in CaV3.1 knockout mice but it is nevertheless recovered by strengthening inhibitory transmission onto PNs; promoting a stronger hyperpolarization via GABAA receptor activation leads to an enhanced availability of an alternative Purkinje-expressed CaV3 isoform compensating for the lack of CaV3.1 and restoring LTP. Accordingly, a stronger hyperpolarization also restores CaV3-mediated calcium influx in PNs from CaV3.1 knockout mice. We conclude that by favoring CaV3 channels availability inhibition promotes LTP at cerebellar excitatory synapses. PMID:27641070

  20. Presynaptic kainate receptors impart an associative property to hippocampal mossy fiber long-term potentiation.

    PubMed

    Schmitz, Dietmar; Mellor, Jack; Breustedt, Joerg; Nicoll, Roger A

    2003-10-01

    Hippocampal mossy fiber synapses show an unusual form of long-term potentiation (LTP) that is independent of NMDA receptor activation and is expressed presynaptically. Using receptor antagonists, as well as receptor knockout mice, we found that presynaptic kainate receptors facilitate the induction of mossy fiber long-term potentiation (LTP), although they are not required for this form of LTP. Most importantly, these receptors impart an associativity to mossy fiber LTP such that activity in neighboring mossy fiber synapses, or even associational/commissural synapses, influences the threshold for inducing mossy fiber LTP. Such a mechanism greatly increases the computational power of this form of plasticity.

  1. Place cells and long-term potentiation in the hippocampus.

    PubMed

    Cobar, Luis Fernando; Yuan, Li; Tashiro, Ayumu

    2017-02-01

    Place cells show location-specific firing patterns according to an animal's position in an environment and are thought to contribute to the spatial representation required for self-navigation. Decades of study have extensively characterized the properties of place cells and suggested the involvement of long-term potentiation (LTP), a long-lasting synaptic strengthening, in place cell activity. Here, we review the basic characteristics of place cell activity and the findings that support the idea that LTP contributes to the formation, maintenance, and plasticity of place cell activity.

  2. MicroRNAs, miR-23a-3p and miR-151-3p, Are Regulated in Dentate Gyrus Neuropil following Induction of Long-Term Potentiation In Vivo

    PubMed Central

    Ryan, Brigid; Logan, Barbara J.; Abraham, Wickliffe C.

    2017-01-01

    Translation of synaptic mRNA contributes to alterations in the proteome necessary to consolidate long-term potentiation (LTP), a model of memory processes. Yet, how this process is controlled is not fully resolved. MicroRNAs are non-coding RNAs that negatively regulate gene expression by suppressing translation or promoting mRNA degradation. As specific microRNAs are synaptically located, we hypothesized that they are ideally suited to couple synaptic activation, translational regulation, and LTP persistence. The aim of this study was to identify LTP-regulated microRNAs at or near synapses. Accordingly, LTP was induced unilaterally at perforant path-dentate gyrus synapses in awake adult Sprague-Dawley rats. Five hours later, dentate gyrus middle molecular layer neuropil, containing potentiated synapses, was laser-microdissected. MicroRNA expression profiling, using TaqMan Low Density MicroRNA Microarrays (n = 4), identified eight regulated microRNAs. Subsequent individual TaqMan assays confirmed upregulation of miR-23a-3p (1.30 ± 0.10; p = 0.015) and miR-151-3p (1.17 ± 0.19; p = 0.045) in a second cohort (n = 7). Interestingly, bioinformatic analysis indicated that miR-151-3p and miR-23a-3p regulate synaptic reorganisation and transcription, respectively. In summary, we have demonstrated for the first time that microRNAs are regulated in isolated neuropil following LTP induction in vivo, supporting the hypothesis that synaptic, LTP-responsive microRNAs contribute to LTP persistence via regulation of the synaptic proteome. PMID:28125614

  3. Potential food-drug interactions in long-term care.

    PubMed

    Anderson, Judy K; Fox, Jodie R

    2012-04-01

    Medication administration at mealtimes may result in food-drug interactions. Older adults are especially at risk of food-drug interactions leading to adverse drug effects and subtherapeutic responses. Research on potential food-drug interactions is limited and dated. This study examined the frequency of potential food-drug interactions in long-term care. Forty-nine percent of drugs administered at mealtimes had potential for interaction, with cardiovascular medications given most frequently. The frequency of potential interactions makes this phenomenon critically important to review. Collaboration between nurses and pharmacists may identify optimal medication scheduling. Nurses can enhance care by identifying strategies to limit interactions through knowledge and creative, collaborative administration schedules.

  4. Long-Term Potentiation: From CaMKII to AMPA Receptor Trafficking.

    PubMed

    Herring, Bruce E; Nicoll, Roger A

    2016-01-01

    For more than 20 years, we have known that Ca(2+)/calmodulin-dependent protein kinase (CaMKII) activation is both necessary and sufficient for the induction of long-term potentiation (LTP). During this time, tremendous effort has been spent in attempting to understand how CaMKII activation gives rise to this phenomenon. Despite such efforts, there is much to be learned about the molecular mechanisms involved in LTP induction downstream of CaMKII activation. In this review, we highlight recent developments that have shaped our current thinking about the molecular mechanisms underlying LTP and discuss important questions that remain in the field.

  5. Erythropoietin enhances hippocampal long-term potentiation and memory

    PubMed Central

    Adamcio, Bartosz; Sargin, Derya; Stradomska, Alicja; Medrihan, Lucian; Gertler, Christoph; Theis, Fabian; Zhang, Mingyue; Müller, Michael; Hassouna, Imam; Hannke, Kathrin; Sperling, Swetlana; Radyushkin, Konstantin; El-Kordi, Ahmed; Schulze, Lizzy; Ronnenberg, Anja; Wolf, Fred; Brose, Nils; Rhee, Jeong-Seop; Zhang, Weiqi; Ehrenreich, Hannelore

    2008-01-01

    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. PMID:18782446

  6. Long-term enhancement (LTE) of postsynaptic potentials following neural conditioning, in mammalian sympathetic ganglia.

    PubMed

    Libet, B; Mochida, S

    1988-11-15

    Orthodromic, preganglionic conditioning stimulation can consistently induce long-term enhancement (LTE) (greater than 3 h) of the muscarinically mediated slow excitatory postsynaptic potential and the slow inhibitory postsynaptic potential. This was shown for superior cervical ganglia of rabbit and rat. Effective conditioning stimuli are in a physiologically observed range (3/s for 7 min, 5/s for 4 min, 10/s for 2 min, 20/s for 1 min). LTE was producible both homosynaptically and heterosynaptically. LTE can thus be associative, with conditioning synaptic input in one line inducing long-term changes in postsynaptic responses to another (heterosynaptic) input. The dopamine antagonist butaclamol depressed LTE, particularly that following the initial postconditioning period of 30 min. Adrenergic antagonists had no effect. This pharmacological evidence, coupled with the heterosynaptic induction of LTE, supports the view that neurally induced LTE may be at least partly mediated by endogenous dopamine. Another non-cholinergic but non-adrenergic transmitter (possibly a peptide) might contribute to the LTE seen in the initial 30 min postconditioning. The present, orthodromically induced LTE is clearly different from the long-term potentiation widely studied in hippocampus, etc., in the modes of induction and synaptic mediation.

  7. Circadian Regulation of Hippocampal Long-Term Potentiation

    PubMed Central

    Chaudhury, Dipesh; Wang, Louisa M.; Colwell, Christopher S.

    2008-01-01

    The goal of this study is to investigate the possible circadian regulation of hippocampal excitability and long-term potentiation (LTP) measured by stimulating the Schaffer collaterals (SC) and recording the field excitatory postsynaptic potential (fEPSP) from the CA1 dendritic layer or the population spike (PS) from the soma in brain slices of C3H and C57 mice. These 2 strains of mice were of interest because the C3H mice secrete melatonin rhythmically while the C57 mice do not. The authors found that the magnitude of the enhancement of the PS was significantly greater in LTP recorded from night slices compared to day slices of both C3H and C57 mice. They also found significant diurnal variation in the decay of LTP measured with fEPSPs, with the decay slower during the night in both strains of mice. There was evidence for a diurnal rhythm in the input/output function of pyramidal neurons measured at the soma in C57 but not C3H mice. Furthermore, LTP in the PS, measured in slices prepared during the day but recorded during the night, had a profile remarkably similar to the night group. Finally, PS recordings were carried out in slices from C3H mice maintained in constant darkness prior to experimentation. Again, the authors found that the magnitude of the enhancement of the PS was significantly greater in LTP recorded from subjective night slices compared to subjective day slices. These results provide the 1st evidence that an endogenous circadian oscillator modulates synaptic plasticity in the hippocampus. PMID:15851529

  8. Postsynaptic density-95 mimics and occludes hippocampal long-term potentiation and enhances long-term depression.

    PubMed

    Stein, Valentin; House, David R C; Bredt, David S; Nicoll, Roger A

    2003-07-02

    Previous studies have shown that overexpression of the protein PSD-95 (postsynaptic density-95) selectively enhances AMPA receptor-mediated synaptic responses in hippocampal pyramidal cells. To determine whether this effect is related to synaptic plasticity at these synapses, we examined whether PSD-95 expression mimics long-term potentiation (LTP), and also whether it influences LTP and long-term depression (LTD) in hippocampal slice cultures. Using simultaneous recording from transfected or infected cells and control pyramidal cells, we found that PSD-95, similar to LTP, increases the amplitude and frequency of miniature EPSCs. It also converts silent synapses to functional synapses, as does LTP. In addition, LTP is completely occluded in cells expressing PSD-95, whereas LTD is greatly enhanced. These results suggest that common mechanisms are involved in controlling synaptic AMPA receptors by PSD-95 and synaptic plasticity.

  9. Long-Term Treatment with Low Doses of Methamphetamine Promotes Neuronal Differentiation and Strengthens Long-Term Potentiation of Glutamatergic Synapses onto Dentate Granule Neurons

    PubMed Central

    Milhazes, Nuno

    2016-01-01

    Abstract Methamphetamine (METH) is a psychostimulant, affecting hippocampal function with disparate cognitive effects, which depends on the dose and time of administration, ranging from improvement to impairment of memory. Importantly, in the United States, METH is approved for the treatment of attention deficit hyperactivity disorder. Modifications of long-term plasticity of synapses originating from the entorhinal cortex onto dentate granule cells (DGCs) have been proposed to underlie cognitive alterations similar to those seen in METH users. However, the effects of METH on synaptic plasticity of the dentate gyrus are unknown. Here, we investigated the impact of long-term administration of METH (2 mg/kg/d) on neurogenesis and synaptic plasticity of immature and mature DGCs of juvenile mice. We used a mouse model of neurogenesis (the G42 line of GAD67-GFP), in which GFP is expressed by differentiating young DGCs. METH treatment enhanced the differentiation of GFP+ cells, as it increased the fraction of GFP+ cells expressing the neuronal marker NeuN, and decreased the amount of immature DGCs coexpressing doublecortin. Interestingly, METH did not change the magnitude of long-term potentiation (LTP) in more immature neurons, but facilitated LTP induction in more differentiated GFP+ and strengthened plasticity in mature GFP− DGCs. The METH-induced facilitation of LTP in GFP+ neurons was accompanied with spine enlargement. Our results reveal a specific action of long-term use of METH in the long-term plasticity of excitatory synapses onto differentiating DGCs and might have important implications toward the understanding of the synaptic basis of METH-induced cognitive alterations. PMID:27419216

  10. Capsaicin-sensitive C- and A-fibre nociceptors control long-term potentiation-like pain amplification in humans.

    PubMed

    Henrich, Florian; Magerl, Walter; Klein, Thomas; Greffrath, Wolfgang; Treede, Rolf-Detlef

    2015-09-01

    Long-term potentiation in the spinal dorsal horn requires peptidergic C-fibre activation in animals. Perceptual correlates of long-term potentiation following high-frequency electrical stimulation in humans include increased sensitivity to electrical stimuli at the high frequency stimulation site (homotopic pain-long-term potentiation) and increased sensitivity to pinprick surrounding the high frequency stimulation site (heterotopic pain-long-term potentiation, equivalent to secondary hyperalgaesia). To characterize the peripheral fibre populations involved in induction of pain-long-term potentiation, we performed two selective nerve block experiments in 30 healthy male volunteers. Functional blockade of TRPV1-positive nociceptors by high-concentration capsaicin (verified by loss of heat pain) significantly reduced pain ratings to high frequency stimulation by 47% (P < 0.001), homotopic pain-long-term potentiation by 71% (P < 0.01), heterotopic pain-long-term potentiation by 92% (P < 0.001) and the area of secondary hyperalgesia by 76% (P < 0.001). The selective blockade of A-fibre conduction by nerve compression (verified by loss of first pain to pinprick) significantly reduced pain ratings to high frequency stimulation by 37% (P < 0.01), but not homotopic pain-long-term potentiation (-5%). It had a marginal effect on heterotopic pain-long-term potentiation (-35%, P = 0.059), while the area of secondary hyperalgesia remained unchanged (-2%, P = 0.88). In conclusion, all nociceptor subclasses contribute to high frequency stimulation-induced pain (with a relative contribution of C > Aδ fibres, and an equal contribution of TRPV1-positive and TRPV1-negative fibres). TRPV1-positive C-fibres are the main inducers of both homotopic and heterotopic pain-long-term potentiation. TRPV1-positive A-fibres contribute substantially to the induction of heterotopic pain-long-term potentiation. TRPV1-negative C-fibres induce a component of homotopic self-facilitation but not

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

    ERIC Educational Resources Information Center

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

    2011-01-01

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

  12. Long-term potentiation and the role of N-methyl-d-aspartate receptors

    PubMed Central

    Volianskis, Arturas; France, Grace; Jensen, Morten S.; Bortolotto, Zuner A.; Jane, David E.; Collingridge, Graham L.

    2015-01-01

    N-methyl-d-aspartate receptors (NMDARs) are known for their role in the induction of long-term potentiation (LTP). Here we start by reviewing the early evidence for their role in LTP at CA1 synapses in the hippocampus. We then discuss more recent evidence that NMDAR dependent synaptic plasticity at these synapses can be separated into mechanistically distinct components. An initial phase of the synaptic potentiation, which is generally termed short-term potentiation (STP), decays in an activity-dependent manner and comprises two components that differ in their kinetics and NMDAR subtype dependence. The faster component involves activation of GluN2A and GluN2B subunits whereas the slower component involves activation of GluN2B and GluN2D subunits. The stable phase of potentiation, commonly referred to as LTP, requires activation of primarily triheteromeric NMDARs containing both GluN2A and GluN2B subunits. In new work, we compare STP with a rebound potentiation (RP) that is induced by NMDA application and conclude that they are different phenomena. We also report that NMDAR dependent long-term depression (NMDAR-LTD) is sensitive to a glycine site NMDAR antagonist. We conclude that NMDARs are not synonymous for either LTP or memory. Whilst important for the induction of LTP at many synapses in the CNS, not all forms of LTP require the activation of NMDARs. Furthermore, NMDARs mediate the induction of other forms of synaptic plasticity and are important for synaptic transmission. It is, therefore, not possible to equate NMDARs with LTP though they are intimately linked. This article is part of a Special Issue entitled SI: Brain and Memory. PMID:25619552

  13. Glutamatergic synapses are structurally and biochemically complex because of multiple plasticity processes: long-term potentiation, long-term depression, short-term potentiation and scaling.

    PubMed

    Lisman, John

    2017-03-05

    Synapses are complex because they perform multiple functions, including at least six mechanistically different forms of plasticity. Here, I comment on recent developments regarding these processes. (i) Short-term potentiation (STP), a Hebbian process that requires small amounts of synaptic input, appears to make strong contributions to some forms of working memory. (ii) The rules for long-term potentiation (LTP) induction in CA3 have been clarified: induction does not depend obligatorily on backpropagating sodium spikes but, rather, on dendritic branch-specific N-methyl-d-aspartate (NMDA) spikes. (iii) Late LTP, a process that requires a dopamine signal (and is therefore neoHebbian), is mediated by trans-synaptic growth of the synapse, a growth that occurs about an hour after LTP induction. (iv) LTD processes are complex and include both homosynaptic and heterosynaptic forms. (v) Synaptic scaling produced by changes in activity levels are not primarily cell-autonomous, but rather depend on network activity. (vi) The evidence for distance-dependent scaling along the primary dendrite is firm, and a plausible structural-based mechanism is suggested.Ideas about the mechanisms of synaptic function need to take into consideration newly emerging data about synaptic structure. Recent super-resolution studies indicate that glutamatergic synapses are modular (module size 70-80 nm), as predicted by theoretical work. Modules are trans-synaptic structures and have high concentrations of postsynaptic density-95 (PSD-95) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor. These modules function as quasi-independent loci of AMPA-mediated transmission and may be independently modifiable, suggesting a new understanding of quantal transmission.This article is part of the themed issue 'Integrating Hebbian and homeostatic plasticity.'

  14. Mapping Gene Expression in Excitatory Neurons during Hippocampal Late-Phase Long-Term Potentiation

    PubMed Central

    Chen, Patrick B.; Kawaguchi, Riki; Blum, Charles; Achiro, Jennifer M.; Coppola, Giovanni; O'Dell, Thomas J.; Martin, Kelsey C.

    2017-01-01

    The persistence of long-lasting changes in synaptic connectivity that underlie long-term memory require new RNA and protein synthesis. To elucidate the temporal pattern of gene expression that gives rise to long-lasting neuronal plasticity, we analyzed differentially-expressed (DE) RNAs in mouse hippocampal slices following induction of late phase long-term potentiation (L-LTP) specifically within pyramidal excitatory neurons using Translating Ribosome Affinity Purification RNA sequencing (TRAP-seq). We detected time-dependent changes in up- and down-regulated ribosome-associated mRNAs over 2 h following L-LTP induction, with minimal overlap of DE transcripts between time points. TRAP-seq revealed greater numbers of DE transcripts and magnitudes of LTP-induced changes than RNA-seq of all cell types in the hippocampus. Neuron-enriched transcripts had greater changes at the ribosome-loading level than the total RNA level, while RNA-seq identified many non-neuronal DE mRNAs. Our results highlight the importance of considering both time course and cell-type specificity in activity-dependent gene expression during memory formation. PMID:28275336

  15. Induction chemoradiation therapy prior to esophagectomy is associated with superior long-term survival for esophageal cancer.

    PubMed

    Speicher, P J; Wang, X; Englum, B R; Ganapathi, A M; Yerokun, B; Hartwig, M G; D'Amico, T A; Berry, M F

    2015-01-01

    The purpose of this study was to examine the role of induction chemoradiation in the treatment of potentially resectable locally advanced (T2-3N0 and T1-3N+) esophageal cancer utilizing a large national database. The National Cancer Data Base (NCDB) was queried for all patients undergoing esophagectomy for clinical T2-3N0 and T1-3N+ esophageal cancer of the mid- or lower esophagus. Patients were stratified by the use of induction chemoradiation therapy versus surgery-first. Trends were assessed with the Cochran-Armitage test. Predictors of receiving induction therapy were evaluated with multivariable logistic regression. A propensity-matched analysis was conducted to compare outcomes between groups, and the Kaplan-Meier method was used to estimate long-term survival. Within the NCDB, 7921 patients were identified, of which 6103 (77.0%) were treated with chemoradiation prior to esophagectomy, while the remaining 1818 (23.0%) were managed with surgery-first. Use of induction therapy increased over time, with an absolute increase of 11.8% from 2003-2011 (P < 0.001). As revealed by the propensity model, induction therapy was associated with higher rates of negative margins and shorter hospital length of stay, but no differences in unplanned readmission and 30-day mortality rates. In unadjusted survival analysis, induction therapy was associated with better long-term survival compared to a strategy of surgery-first, with 5-year survival rates of 37.2% versus 28.6%, P < 0.001. Following propensity score matching analysis, the use of induction therapy maintained a significant survival advantage over surgery-first (5-year survival: 37.9% vs. 28.7%, P < 0.001). Treatment with induction chemoradiation therapy prior to surgical resection is associated with significant improvement in long-term survival, even after adjusting for confounders with a propensity model. Induction therapy should be considered in all medically appropriate patients with resectable cT2-3N0 and cT1-3N

  16. Epinephrine converts long-term potentiation from transient to durable form in awake rats.

    PubMed

    Korol, D L; Gold, P E

    2008-01-01

    Neuroendocrine responses to an emotional or arousing experience modulate memory for the event. Extensive evidence suggests that epinephrine plays an important role in the regulation of memory formation by emotions and arousal. Some forms of synaptic plasticity are similarly responsive to modulation by stress and arousal. The present experiment examined the effects of epinephrine on induction and maintenance of long-term potentiation (LTP) in awake rats. Rats were prepared with bilaterally implanted electrodes for recording evoked field potentials in dentate granule cells following perforant pathway stimulation. LTP was induced with high-frequency stimulation parameters that resulted in modest early potentiation of the EPSP that decayed within 20 min. Epinephrine enhanced the magnitude of early LTP induction and also extended the durability of LTP from minutes to at least several days. Epinephrine did not alter baseline responses or modulate pre-LTP input-output curves. The enhancement of LTP by epinephrine was dose-dependent, following an inverted-U dose-response curve similar to that seen in memory enhancement experiments, suggesting considerable convergence of epinephrine modulation of memory and LTP. In extending substantially the maintenance of LTP after induction, the present finding offer potential means to study the neurobiology of rapid forgetting seen in aged rodents and other animals and the neurobiology of the impaired forgetting seen in post-traumatic stress disorder.

  17. Multiple cellular cascades participate in long-term potentiation and in hippocampus-dependent learning

    PubMed Central

    Baudry, Michel; Zhu, Guoqi; Liu, Yan; Wang, Yubin; Briz, Victor; Bi, Xiaoning

    2015-01-01

    Since its discovery by Bliss and Lomo, the phenomenon of long-term potentiation (LTP) has been extensively studied, as it was viewed as a potential cellular mechanism of learning and memory. Over the years, many signaling cascades have been implicated in its induction, consolidation and maintenance, raising questions regarding its real significance. Here, we review several of the most commonly studies signaling cascades and discuss how they converge on a common set of mechanisms likely to be involved in the maintenance of LTP. We further argue that the existence of cross-talks between these different signaling cascades can not only account for several discrepancies in the literature, but also account for the existence of different forms of LTP, which can be engaged by different types of stimulus parameters under different experimental conditions. Finally, we discuss how the understanding of the diversity of LTP mechanisms can help us understand the diversity of the types of learning and memory. PMID:25482663

  18. Heterogeneous spatial patterns of long-term potentiation in rat hippocampal slices

    PubMed Central

    Chang, Payne Y; Jackson, Meyer B

    2006-01-01

    Although LTP (long-term potentiation) of synaptic transmission has received much attention as a model for learning and memory, its function within a neural circuit context remains poorly understood. To monitor LTP over an extensive circuit, we imaged responses in hippocampal slices using a voltage-sensitive dye. Following theta-burst stimulation, evoked optical signals showed an increase that lasted 40 min or more. Weak stimuli only potentiated the local area around the stimulating electrode, but stronger stimuli induced LTP over a wide area with a complex and non-uniform spatial pattern. The expression of LTP showed distinct peaks and valleys that depended on which axons were activated. Interestingly, the spatial distribution of LTP bore no relation to the spatial distribution of single-shock responses, but closely resembled the distribution of postsynaptic spikes evoked by theta bursts. Thus, postsynaptic spikes during induction constitute a critical determinant for the expression of LTP in intact circuits. PMID:16873414

  19. Inhibition of TRPV1 channels enables long-term potentiation in the entorhinal cortex.

    PubMed

    Banke, Tue G

    2016-04-01

    The transient receptor potential vanilloid 1 (TRPV1) channel is a non-selective cation channel that is mainly found in nociceptive neurons of the peripheral nervous system; however, these channels have also been located within the CNS, including the entorhinal cortex. Whole-cell patch-clamp recordings of principal entorhinal cortex (EC) layers II/III neurons revealed that evoked inhibitory postsynaptic currents were depressed by application of the TRPV1 agonist capsaicin (CAP), accompanied by a change in the pair-pulse ratio (PPR). In addition, recordings of miniature inhibitory postsynaptic currents (mIPSCs) revealed that inter-event intervals but not amplitude were decreased in wild-type (WT) after application of CAP. This suggests that TRPV1 channels are functional in the entorhinal cortex and are located on inhibitory neurons with their axonal arborization within layers II/III. In order to study TRPV1 channels and their involvement in long-term potentiation (LTP) induction in a more intact circuit, extracellular field potential recordings were performed in EC layers II/III. It was found that activated TRPV1 channels preclude induction of long-term potentiation. In sharp contrast, clear LTP was observed when antagonizing TRPV1 channels or recording from TRPV1 knock-out mice. Thus, these results suggests that signaling through activating inhibitory presynaptic TRPV1 channels represents a novel mechanism by which a shift in feed-forward inhibition of layers II/III cortical principal neurons prompt changes in synaptic strength and thereby contribute to a change of information storage within the brain.

  20. β-Adrenergic receptor signaling and modulation of long-term potentiation in the mammalian hippocampus.

    PubMed

    O'Dell, Thomas J; Connor, Steven A; Guglietta, Ryan; Nguyen, Peter V

    2015-09-01

    Encoding new information in the brain requires changes in synaptic strength. Neuromodulatory transmitters can facilitate synaptic plasticity by modifying the actions and expression of specific signaling cascades, transmitter receptors and their associated signaling complexes, genes, and effector proteins. One critical neuromodulator in the mammalian brain is norepinephrine (NE), which regulates multiple brain functions such as attention, perception, arousal, sleep, learning, and memory. The mammalian hippocampus receives noradrenergic innervation and hippocampal neurons express β-adrenergic receptors, which are known to play important roles in gating the induction of long-lasting forms of synaptic potentiation. These forms of long-term potentiation (LTP) are believed to importantly contribute to long-term storage of spatial and contextual memories in the brain. In this review, we highlight the contributions of noradrenergic signaling in general and β-adrenergic receptors in particular, toward modulating hippocampal LTP. We focus on the roles of NE and β-adrenergic receptors in altering the efficacies of specific signaling molecules such as NMDA and AMPA receptors, protein phosphatases, and translation initiation factors. Also, the roles of β-adrenergic receptors in regulating synaptic "tagging" and "capture" of LTP within synaptic networks of the hippocampus are reviewed. Understanding the molecular and cellular bases of noradrenergic signaling will enrich our grasp of how the brain makes new, enduring memories, and may shed light on credible strategies for improving mental health through treatment of specific disorders linked to perturbed memory processing and dysfunctional noradrenergic synaptic transmission.

  1. Dopaminergic neurotransmission dysfunction induced by amyloid-β transforms cortical long-term potentiation into long-term depression and produces memory impairment.

    PubMed

    Moreno-Castilla, Perla; Rodriguez-Duran, Luis F; Guzman-Ramos, Kioko; Barcenas-Femat, Alejandro; Escobar, Martha L; Bermudez-Rattoni, Federico

    2016-05-01

    Alzheimer's disease (AD) is a neurodegenerative condition manifested by synaptic dysfunction and memory loss, but the mechanisms underlying synaptic failure are not entirely understood. Although dopamine is a key modulator of synaptic plasticity, dopaminergic neurotransmission dysfunction in AD has mostly been associated to noncognitive symptoms. Thus, we aimed to study the relationship between dopaminergic neurotransmission and synaptic plasticity in AD models. We used a transgenic model of AD (triple-transgenic mouse model of AD) and the administration of exogenous amyloid-β (Aβ) oligomers into wild type mice. We found that Aβ decreased cortical dopamine levels and converted in vivo long-term potentiation (LTP) into long-term depression (LTD) after high-frequency stimulation delivered at basolateral amygdaloid nucleus-insular cortex projection, which led to impaired recognition memory. Remarkably, increasing cortical dopamine and norepinephrine levels rescued both high-frequency stimulation -induced LTP and memory, whereas depletion of catecholaminergic levels mimicked the Aβ-induced shift from LTP to LTD. Our results suggest that Aβ-induced dopamine depletion is a core mechanism underlying the early synaptopathy and memory alterations observed in AD models and acts by modifying the threshold for the induction of cortical LTP and/or LTD.

  2. Hippocampal CA1 Kindling but Not Long-Term Potentiation Disrupts Spatial Memory Performance

    ERIC Educational Resources Information Center

    Leung, L. Stan; Shen, Bixia

    2006-01-01

    Long-term synaptic enhancement in the hippocampus has been suggested to cause deficits in spatial performance. Synaptic enhancement has been reported after hippocampal kindling that induced repeated electrographic seizures or afterdischarges (ADs) and after long-term potentiation (LTP) defined as synaptic enhancement without ADs. We studied…

  3. SGK Protein Kinase Facilitates the Expression of Long-Term Potentiation in Hippocampal Neurons

    ERIC Educational Resources Information Center

    Ma, Yun L.; Tsai, Ming C.; Hsu, Wei L.; Lee, Eminy H.Y.

    2006-01-01

    Previous studies showed that the serum- and glucocorticoid-inducible kinase ("sgk") gene plays an important role in long-term memory formation. The present study further examined the role of SGK in long-term potentiation (LTP). The dominant-negative mutant of "sgk," SGKS422A, was used to inactivate SGK. Results revealed a time-dependent increase…

  4. Integrin Dynamics Produce a Delayed Stage of Long-Term Potentiation and Memory Consolidation

    PubMed Central

    Babayan, Alex H.; Kramár, Enikö A.; Barrett, Ruth M.; Jafari, Matiar; Häettig, Jakob; Chen, Lulu Y.; Rex, Christopher S.; Lauterborn, Julie C.; Wood, Marcelo A.; Gall, Christine M.

    2012-01-01

    Memory consolidation theory posits that newly acquired information passes through a series of stabilization steps before being firmly encoded. We report here that in rat and mouse, hippocampus cell adhesion receptors belonging to the β1-integrin family exhibit dynamic properties in adult synapses and that these contribute importantly to a previously unidentified stage of consolidation. Quantitative dual immunofluorescence microscopy showed that induction of long-term potentiation (LTP) by theta burst stimulation (TBS) activates β1 integrins, and integrin-signaling kinases, at spine synapses in adult hippocampal slices. Neutralizing antisera selective for β1 integrins blocked these effects. TBS-induced integrin activation was brief (<7 min) and followed by an ∼45 min period during which the adhesion receptors did not respond to a second application of TBS. Brefeldin A, which blocks integrin trafficking to the plasma membrane, prevented the delayed recovery of integrin responses to TBS. β1 integrin-neutralizing antisera erased LTP when applied during, but not after, the return of integrin responsivity. Similarly, infusions of anti-β1 into rostral mouse hippocampus blocked formation of long-term, object location memory when started 20 min after learning but not 40 min later. The finding that β1 integrin neutralization was effective in the same time window for slice and behavioral experiments strongly suggests that integrin recovery triggers a temporally discrete, previously undetected second stage of consolidation for both LTP and memory. PMID:22973009

  5. Dynamical properties of gene regulatory networks involved in long-term potentiation

    PubMed Central

    Nido, Gonzalo S.; Ryan, Margaret M.; Benuskova, Lubica; Williams, Joanna M.

    2015-01-01

    The long-lasting enhancement of synaptic effectiveness known as long-term potentiation (LTP) is considered to be the cellular basis of long-term memory. LTP elicits changes at the cellular and molecular level, including temporally specific alterations in gene networks. LTP can be seen as a biological process in which a transient signal sets a new homeostatic state that is “remembered” by cellular regulatory systems. Previously, we have shown that early growth response (Egr) transcription factors are of fundamental importance to gene networks recruited early after LTP induction. From a systems perspective, we hypothesized that these networks will show less stable architecture, while networks recruited later will exhibit increased stability, being more directly related to LTP consolidation. Using random Boolean network (RBN) simulations we found that the network derived at 24 h was markedly more stable than those derived at 20 min or 5 h post-LTP. This temporal effect on the vulnerability of the networks is mirrored by what is known about the vulnerability of LTP and memory itself. Differential gene co-expression analysis further highlighted the importance of the Egr family and found a rapid enrichment in connectivity at 20 min, followed by a systematic decrease, providing a potential explanation for the down-regulation of gene expression at 24 h documented in our preceding studies. We also found that the architecture exhibited by a control and the 24 h LTP co-expression networks fit well to a scale-free distribution, known to be robust against perturbations. By contrast the 20 min and 5 h networks showed more truncated distributions. These results suggest that a new homeostatic state is achieved 24 h post-LTP. Together, these data present an integrated view of the genomic response following LTP induction by which the stability of the networks regulated at different times parallel the properties observed at the synapse. PMID:26300724

  6. Hippocampal long-term potentiation is not accompanied by presynaptic spike broadening, unlike synaptic potentiation by K+ channel blockers.

    PubMed

    Laerum, H; Storm, J F

    1994-02-21

    The expression of hippocampal long-term potentiation (LTP) is thought to be at least partly due to increased transmitter release. To test whether this increase is due to a broadening of the presynaptic action potential, we have compared the presynaptic fibre volley before and after LTP induction, or application of K+ channel blockers, in CA1 of rat hippocampal slices. Tetraethylammonium (TEA; 1 mM) induced a parallel increase in the fibre volley duration of the slope of the field EPSP, indicating that a presynaptic spike broadening underlying synaptic potentiation can be detected. In contrast, induction of LTP did not produce any measurable change in the fibre volley, although the average increase in the EPSP slope was larger than with TEA. These results indicate that LTP expression is not primarily due to a presynaptic spike broadening.

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

    PubMed Central

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

    2016-01-01

    PKMζ is a persistently active PKC isoform proposed to maintain late-LTP and long-term memory. But late-LTP and memory are maintained without PKMζ in PKMζ-null mice. Two hypotheses can account for these findings. First, PKMζ is unimportant for LTP or memory. Second, PKMζ is essential for late-LTP and long-term memory in wild-type mice, and PKMζ-null mice recruit compensatory mechanisms. We find that whereas PKMζ persistently increases in LTP maintenance in wild-type mice, PKCι/λ, a gene-product closely related to PKMζ, persistently increases in LTP maintenance in PKMζ-null mice. Using a pharmacogenetic approach, we find PKMζ-antisense in hippocampus blocks late-LTP and spatial long-term memory in wild-type mice, but not in PKMζ-null mice without the target mRNA. Conversely, a PKCι/λ-antagonist disrupts late-LTP and spatial memory in PKMζ-null mice but not in wild-type mice. Thus, whereas PKMζ is essential for wild-type LTP and long-term memory, persistent PKCι/λ activation compensates for PKMζ loss in PKMζ-null mice. DOI: http://dx.doi.org/10.7554/eLife.14846.001 PMID:27187150

  8. The phosphatase SHP2 regulates the spacing effect for long-term memory induction.

    PubMed

    Pagani, Mario R; Oishi, Kimihiko; Gelb, Bruce D; Zhong, Yi

    2009-10-02

    A property of long-term memory (LTM) induction is the requirement for repeated training sessions spaced over time. This augmentation of memory formation with spaced resting intervals is called the spacing effect. We now show that in Drosophila, the duration of resting intervals required for inducing LTM is regulated by activity levels of the protein tyrosine phosphatase corkscrew (CSW). Overexpression of wild-type CSW in mushroom body neurons shortens the inter-trial interval required for LTM induction, whereas overexpression of constitutively active CSW proteins prolongs these resting intervals. These gain-of-function csw mutations are associated with a clinical condition of mental retardation. Biochemical analysis reveals that LTM-inducing training regimens generate repetitive waves of CSW-dependent MAPK activation, the length of which appears to define the duration of the resting interval. Constitutively active CSW proteins prolong the resting interval by altering the MAPK inactivation cycle. We thus provide insight into the molecular basis of the spacing effect.

  9. Dendritic K+ channels contribute to spike-timing dependent long-term potentiation in hippocampal pyramidal neurons

    PubMed Central

    Watanabe, Shigeo; Hoffman, Dax A.; Migliore, Michele; Johnston, Daniel

    2002-01-01

    We investigated the role of A-type K+ channels for the induction of long-term potentiation (LTP) of Schaffer collateral inputs to hippocampal CA1 pyramidal neurons. When low-amplitude excitatory postsynaptic potentials (EPSPs) were paired with two postsynaptic action potentials in a theta-burst pattern, N-methyl-d-aspartate (NMDA)-receptor-dependent LTP was induced. The amplitudes of the back-propagating action potentials were boosted in the dendrites only when they were coincident with the EPSPs. Mitogen-activated protein kinase (MAPK) inhibitors PD 098059 or U0126 shifted the activation of dendritic K+ channels to more hyperpolarized potentials, reduced the boosting of dendritic action potentials by EPSPs, and suppressed the induction of LTP. These results support the hypothesis that dendritic K+ channels and the boosting of back-propagating action potentials contribute to the induction of LTP in CA1 neurons. PMID:12048251

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

    NASA Astrophysics Data System (ADS)

    Sengupta, Abhronil; Roy, Kaushik

    2016-02-01

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

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

    PubMed Central

    2011-01-01

    Long-term potentiation (LTP) in nociceptive spinal pathways shares several features with hyperalgesia and has been proposed to be a cellular mechanism of pain amplification in acute and chronic pain states. Spinal LTP is typically induced by noxious input and has therefore been hypothesized to contribute to acute postoperative pain and to forms of chronic pain that develop from an initial painful event, peripheral inflammation or neuropathy. Under this assumption, preventing LTP induction may help to prevent the development of exaggerated postoperative pain and reversing established LTP may help to treat patients who have an LTP component to their chronic pain. Spinal LTP is also induced by abrupt opioid withdrawal, making it a possible mechanism of some forms of opioid-induced hyperalgesia. Here, we give an overview of targets for preventing LTP induction and modifying established LTP as identified in animal studies. We discuss which of the various symptoms of human experimental and clinical pain may be manifestations of spinal LTP, review the pharmacology of these possible human LTP manifestations and compare it to the pharmacology of spinal LTP in rodents. PMID:21443797

  12. Postsynaptic Signal Transduction Models for Long-Term Potentiation and Depression

    PubMed Central

    Manninen, Tiina; Hituri, Katri; Kotaleski, Jeanette Hellgren; Blackwell, Kim T.; Linne, Marja-Leena

    2010-01-01

    More than a hundred biochemical species, activated by neurotransmitters binding to transmembrane receptors, are important in long-term potentiation (LTP) and long-term depression (LTD). To investigate which species and interactions are critical for synaptic plasticity, many computational postsynaptic signal transduction models have been developed. The models range from simple models with a single reversible reaction to detailed models with several hundred kinetic reactions. In this study, more than a hundred models are reviewed, and their features are compared and contrasted so that similarities and differences are more readily apparent. The models are classified according to the type of synaptic plasticity that is modeled (LTP or LTD) and whether they include diffusion or electrophysiological phenomena. Other characteristics that discriminate the models include the phase of synaptic plasticity modeled (induction, expression, or maintenance) and the simulation method used (deterministic or stochastic). We find that models are becoming increasingly sophisticated, by including stochastic properties, integrating with electrophysiological properties of entire neurons, or incorporating diffusion of signaling molecules. Simpler models continue to be developed because they are computationally efficient and allow theoretical analysis. The more complex models permit investigation of mechanisms underlying specific properties and experimental verification of model predictions. Nonetheless, it is difficult to fully comprehend the evolution of these models because (1) several models are not described in detail in the publications, (2) only a few models are provided in existing model databases, and (3) comparison to previous models is lacking. We conclude that the value of these models for understanding molecular mechanisms of synaptic plasticity is increasing and will be enhanced further with more complete descriptions and sharing of the published models. PMID:21188161

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

    PubMed

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

    2010-10-30

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

  14. Endocannabinoid-Dependent Long-Term Potentiation of Synaptic Transmission at Rat Barrel Cortex.

    PubMed

    Maglio, Laura Eva; Noriega-Prieto, José Antonio; Maraver, Maria Jesús; Fernández de Sevilla, David

    2017-03-01

    Brain-derived neurotrophic factor (BDNF) plays a critical role in modulating plasticity in sensory cortices. Indeed, a BDNF-dependent long-term potentiation (LTP) at distal basal excitatory synapses of Layer 5 pyramidal neurons (L5PNs) has been demonstrated in disinhibited rat barrel cortex slices. Although it is well established that this LTP requires the pairing of excitatory postsynaptic potentials (PSPs) with Ca2+ spikes, its induction when synaptic inhibition is working remains unexplored. Here we show that low-frequency stimulation at basal dendrites of L5PNs is able to trigger a PSP followed by an action potential (AP) and a slow depolarization (termed PSP-Ca2+ response) in thalamocortical slices without blocking synaptic inhibition. We demonstrate that AP barrage-mediated release of endocannabinoids (eCBs) from the recorded L5PNs induces PSP-Ca2+ response facilitation and BDNF-dependent LTP. Indeed, this LTP requires the type 1 cannabinoid receptors activation, is prevented by postsynaptic intracellular 1,2-bis(2-aminophenoxy) ethane-N,N,N,N'-tetraacetic acid (BAPTA) or the anandamide membrane transporter inhibitor AM404, and only occurs in L5PNs neurons showing depolarization-induced suppression of inhibition. Additionally, electrical stimulation at the posteromedial thalamic nucleus induced similar response and LTP. These results reveal a novel form of eCB-dependent LTP at L5PNs that could be relevant in the processing of sensory information in the barrel cortex.

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

    PubMed Central

    Prestori, Francesca; Bonardi, Claudia; Mapelli, Lisa; Lombardo, Paola; Goselink, Rianne; De Stefano, Maria Egle; Gandolfi, Daniela; Mapelli, Jonathan; Bertrand, Daniel; Schonewille, Martijn; De Zeeuw, Chris; D’Angelo, Egidio

    2013-01-01

    The brain needs mechanisms able to correlate plastic changes with local circuit activity and internal functional states. At the cerebellum input stage, uncontrolled induction of long-term potentiation or depression (LTP or LTD) between mossy fibres and granule cells can saturate synaptic capacity and impair cerebellar functioning, which suggests that neuromodulators are required to gate plasticity processes. Cholinergic systems innervating the cerebellum are thought to enhance procedural learning and memory. Here we show that a specific subtype of acetylcholine receptors, the α7-nAChRs, are distributed both in cerebellar mossy fibre terminals and granule cell dendrites and contribute substantially to synaptic regulation. Selective α7-nAChR activation enhances the postsynaptic calcium increase, allowing weak mossy fibre bursts, which would otherwise cause LTD, to generate robust LTP. The local microperfusion of α7-nAChR agonists could also lead to in vivo switching of LTD to LTP following sensory stimulation of the whisker pad. In the cerebellar flocculus, α7-nAChR pharmacological activation impaired vestibulo-ocular-reflex adaptation, probably because LTP was saturated, preventing the fine adjustment of synaptic weights. These results show that gating mechanisms mediated by specific subtypes of nicotinic receptors are required to control the LTD/LTP balance at the mossy fibre-granule cell relay in order to regulate cerebellar plasticity and behavioural adaptation. PMID:23741401

  16. 12-lipoxygenase regulates hippocampal long-term potentiation by modulating L-type Ca2+ channels

    PubMed Central

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

    2010-01-01

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

  17. Zinc-mediated attenuation of hippocampal mossy fiber long-term potentiation induced by forskolin.

    PubMed

    Ando, Masaki; Oku, Naoto; Takeda, Atsushi

    2010-11-01

    The rise in presynaptic calcium induced by high-frequency stimulation activates the calcium-calmodulin-sensitive adenylyl cyclase (AC) 1 followed by the induction of long-term potentiation (LTP) at the hippocampal mossy fiber-CA3 synapse. Zinc is released with glutamate from mossy fiber terminals. However, the role of the zinc in mossy fiber LTP is controversial. In the present study, the mechanism of zinc-mediated attenuation of mossy fiber LTP was examined in that induced by forskolin, an AC activator. Mossy fiber LTP induced by tetanic stimulation (100 Hz for 1 s) was attenuated in the presence of 5 microM ZnCl(2), whereas that induced by forskolin under test stimulation (0.1 Hz) was not attenuated. Forskolin-induced mossy fiber LTP was attenuated by perfusion with 100 microM ZnCl(2) prior to the induction. However, the zinc (100 microM) pre-perfusion did not attenuate mossy fiber LTP induced by Sp-cAMPS, an activator of protein kinase A, under test stimulation. Zinc is necessary to be taken up into mossy fiber boutons for effectively inhibiting AC activity. In hippocampal slices labeled with ZnAF-2 DA, a membrane-permeable zinc indicator, intracellular ZnAF-2 signal was increased during tetanic stimulation in the presence of 5 microM ZnCl(2), but not under test stimulation. Intracellular ZnAF-2 signal was increased under test stimulation in the presence of 100 microM ZnCl(2). These results suggest that zinc taken up into mossy fibers attenuates forskolin-induced mossy fiber LTP via inhibition of AC activity. The significance of endogenous zinc uptake by mossy fibers is discussed focused on tetanus-induced mossy fiber LTP.

  18. Orexin A induces bidirectional modulation of synaptic plasticity: Inhibiting long-term potentiation and preventing depotentiation.

    PubMed

    Lu, Guan-Ling; Lee, Chia-Hsu; Chiou, Lih-Chu

    2016-08-01

    The orexin system consists of two peptides, orexin A and B and two receptors, OX1R and OX2R. It is implicated in learning and memory regulation while controversy remains on its role in modulating hippocampal synaptic plasticity in vivo and in vitro. Here, we investigated effects of orexin A on two forms of synaptic plasticity, long-term potentiation (LTP) and depotentiation of field excitatory postsynaptic potentials (fEPSPs), at the Schaffer Collateral-CA1 synapse of mouse hippocampal slices. Orexin A (≧30 nM) attenuated LTP induced by theta burst stimulation (TBS) in a manner antagonized by an OX1R (SB-334867), but not OX2R (EMPA), antagonist. Conversely, at 1 pM, co-application of orexin A prevented the induction of depotentiation induced by low frequency stimulation (LFS), i.e. restoring LTP. This re-potentiation effect of sub-nanomolar orexin A occurred at LFS of 1 Hz, but not 2 Hz, and with LTP induced by either TBS or tetanic stimulation. It was significantly antagonized by SB-334867, EMPA and TCS-1102, selective OX1R, OX2R and dual OXR antagonists, respectively, and prevented by D609, SQ22536 and H89, inhibitors of phospholipase C (PLC), adenylyl cyclase (AC) and protein kinase A (PKA), respectively. LFS-induced depotentiation was antagonized by blockers of NMDA, A1-adenosine and type 1/5 metabotropic glutamate (mGlu1/5) receptors, respectively. However, orexin A (1 pM) did not affect chemical-induced depotentiation by agonists of these receptors. These results suggest that orexin A bidirectionally modulates hippocampal CA1 synaptic plasticity, inhibiting LTP via OX1Rs at moderate concentrations while inducing re-potentiation via OX1Rs and OX2Rs, possibly through PLC and AC-PKA signaling at sub-nanomolar concentrations.

  19. Assessment of different induction protocols to elicit long-term depression (LTD) in the rat visual cortex in vivo.

    PubMed

    Hager, Audrey M; Dringenberg, Hans C

    2010-03-08

    Changes in synaptic efficacy, including long-term potentiation (LTP) and long-term depression (LTD), provide mechanisms for experience-induced plasticity of cortical and subcortical circuits. LTP is readily induced under drastically different experimental conditions (e.g., in vitro and in vivo). However, few studies have compared the effectiveness of different induction protocols to elicit synaptic depression, especially under in vivo conditions. Here, we assessed the effectiveness of four different low frequency stimulation (LFS) protocols, applied to the lateral geniculate nucleus, to induce LTD-like changes of local field postsynaptic potentials (fPSPs) recorded on the surface of the primary visual cortex (V1) of urethane-anesthetized rats. Three LFS protocols (900 pulses at 1 Hz; 1800 pulses at 1 Hz, 1800 pulses at 1 Hz, repeated three times), known to induce LTD in neocortical and hippocampal slice preparations, failed to induce synaptic depression. In contrast, strong low frequency burst stimulation (3 pulses/burst at 20 Hz, 900 bursts repeated at 1 Hz) resulted in significant, but transient ( approximately 20 min) depression of fPSPs in V1. This effect was resistant to systemic treatment with MK 801 (0.5 mg/kg) or local, cortical application of either APV (10 mM) or MCPG (10 mM), indicative of non-essential roles of N-methyl-d-aspartate and metabotropic glutamate receptors. A similar depressant effect was also observed under sodium pentobarbital anesthesia. These experiments emphasize the resistance of the in vivo neocortex to express the long-lasting down-regulation of synaptic strength, observations that require integration into current models and theories regarding the functions of LTD as a homeostatic and experience-dependent plasticity mechanism.

  20. Long-term potentiation in the hippocampus of fragile X knockout mice

    SciTech Connect

    Godfraind, J.M.; Reyniers, E.; De Boulle, K.

    1996-08-09

    To gain more insight in the physiological function of the fragile X gene (FMR1) and the mechanisms leading to fragile X syndrome, the Fmr1 gene has been inactivated in mice by gene targeting techniques. In the Morris water maze test, the Fmr1 knockout mice learn to find the hidden platform nearly as well as the control animals, but show impaired performance after the position of the platform has been modified. As malperformance in the Morris water maze test has been associated with impaired long-term potentiation (LTP), electrophysiological studies were performed in hippocampal slices of Fmr1 knockout mice to check for the presence of LTP. Judged by field extracellular excitatory postsynaptic potential recordings in the CA1 hippocampal area, Fmr1 knockout mice express LTP to a similar extent as their wild type littermates during the first 1-2 hr after high frequency stimulation. Also, short-term potentiation (STP) was similar in both types of mice. To investigate whether Fmr1 is involved in the latter stages of LTP as an immediate early gene, we compared Fmr1 mRNA quantities on northern blots after chemical induction of seizures. A transient increase in the transcription of immediate early genes is thought to be essential for the maintenance of LTP. As no increase in Fmr1 mRNA could be detected, neither in cortex nor in total brain, during the first 2{1/2} hr after pentylenetetrazol-induced seizures, it is unlikely that Fmr1 is an immediate early gene in mice. In conclusion, we found no evidence for a function of FMR1 in STP or LTP. 37 refs., 4 figs.

  1. A presynaptic locus for long-term potentiation of elementary synaptic transmission at mossy fiber synapses in culture.

    PubMed Central

    López-García, J C; Arancio, O; Kandel, E R; Baranes, D

    1996-01-01

    The complex circuitry of the CA3 region and the abundance of collateral connections has made it difficult to study the mossy fiber pathway in hippocampal slices and therefore to establish the site of expression of long-term potentiation at these synapses. Using a novel cell culture system, we have produced long-term potentiation of the elementary synaptic connections on single CA3 pyramidal neurons following tetanic stimulation of individual dentate gyrus granule cells. As is the case for the hippocampal slice, this potentiation was independent of N-methyl-D-aspartate receptor activation, was simulated by application of forskolin, and its induction did not require any modulatory input. The increase in synaptic strength was accompanied by a reduction in the number of failures of transmission and by an increase in the coefficient of variation of the responses and was prevented by presynaptic injection of an inhibitor of protein kinase A. These findings show that mossy fiber long-term potentiation has a presynaptic locus and that its expression is dependent on protein kinase A. PMID:8643468

  2. Bone induction using demineralized bone in the rabbit femur: a long-term study.

    PubMed

    Concannon, M J; Boschert, M T; Puckett, C L

    1997-06-01

    While traditional bone grafting is the standard for replacement of segmental bony defects, alternative options (avoiding morbidity of autologous grafts) are attractive and continue to be sought. This study attempted to determine whether demineralized bone powder could be used reliably to replace a significant bony deficit at a weight-bearing site. The long-term functional characteristics of this induced bone were analyzed to determine whether it maintained its strength and shape and reacted normally to physiologic stress over an extended period of time (12 months). In 55 New Zealand White rabbits, a 1-cm length of femur was removed (approximately 20 percent of the total length of the rabbit femur). The femur was then reconstructed with a titanium mandibular plate, leaving the gap intact. In 38 of the animals, this gap was filled with demineralized bone powder in an attempt to induce bone to form across the defect. In group 1 (n = 23), the mandibular plate remained in place for the duration of the study (12 months). In group 2 (n = 15), the plate was removed 8 weeks after placement of the demineralized bone powder, and the animals were followed for an additional 12 months. In group 3 (n = 10), nothing was placed within the bony gap. In group 4 (n = 7), the gap was repaired with autologous bone graft. All the animals that received demineralized bone powder completely filled the osteotomy gap with new bone within 6 to 8 weeks after implantation. None of control group 3 formed bone across the gap (p < 0.001). Eighty-six percent of control group 4 (autologous bone graft) successfully formed bone across the osteotomy gap. In addition, 90 percent of control group 3 had hardware failure within 8 weeks after surgery compared with 0 percent (0 of 38) of the group that received demineralized bone powder (p < 0.001). In group 1, analysis after 12 months revealed that the bone formed ultimately became thin and easily fractured, most likely because of shielding from stress

  3. Enhanced AMPA Receptor Function Promotes Cerebellar Long-Term Depression Rather than Potentiation

    ERIC Educational Resources Information Center

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

    2014-01-01

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

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

    ERIC Educational Resources Information Center

    Vedder, Lindsey C.; Savage, Lisa M.

    2017-01-01

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

  5. Synapse Specificity of Long-Term Potentiation Breaks Down with Aging

    ERIC Educational Resources Information Center

    Ris, Laurence; Godaux, Emile

    2007-01-01

    Memory shows age-related decline. According to the current prevailing theoretical model, encoding of memories relies on modifications in the strength of the synapses connecting the different cells within a neuronal network. The selective increases in synaptic weight are thought to be biologically implemented by long-term potentiation (LTP). Here,…

  6. Induction of Long-term Depression-like Plasticity by Pairings of Motor Imagination and Peripheral Electrical Stimulation.

    PubMed

    Jochumsen, Mads; Signal, Nada; Nedergaard, Rasmus W; Taylor, Denise; Haavik, Heidi; Niazi, Imran K

    2015-01-01

    Long-term depression (LTD) and long-term potentiation (LTP)-like plasticity are models of synaptic plasticity which have been associated with memory and learning. The induction of LTD and LTP-like plasticity, using different stimulation protocols, has been proposed as a means of addressing abnormalities in cortical excitability associated with conditions such as focal hand dystonia and stroke. The aim of this study was to investigate whether the excitability of the cortical projections to the tibialis anterior (TA) muscle could be decreased when dorsiflexion of the ankle joint was imagined and paired with peripheral electrical stimulation (ES) of the nerve supplying the antagonist soleus muscle. The effect of stimulus timing was evaluated by comparing paired stimulation timed to reach the cortex before, at and after the onset of imagined movement. Fourteen healthy subjects participated in six experimental sessions held on non-consecutive days. The timing of stimulation delivery was determined offline based on the contingent negative variation (CNV) of electroencephalography brain data obtained during imagined dorsiflexion. Afferent stimulation was provided via a single pulse ES to the peripheral nerve paired, based on the CNV, with motor imagination of ankle dorsiflexion. A significant decrease (P = 0.001) in the excitability of the cortical projection of TA was observed when the afferent volley from the ES of the tibial nerve (TN) reached the cortex at the onset of motor imagination based on the CNV. When TN stimulation was delivered before (P = 0.62), or after (P = 0.23) imagined movement onset there was no significant effect. Nor was a significant effect found when ES of the TN was applied independent of imagined movement (P = 0.45). Therefore, the excitability of the cortical projection to a muscle can be inhibited when ES of the nerve supplying the antagonist muscle is precisely paired with the onset of imagined movement.

  7. Induction of Long-term Depression-like Plasticity by Pairings of Motor Imagination and Peripheral Electrical Stimulation

    PubMed Central

    Jochumsen, Mads; Signal, Nada; Nedergaard, Rasmus W.; Taylor, Denise; Haavik, Heidi; Niazi, Imran K.

    2015-01-01

    Long-term depression (LTD) and long-term potentiation (LTP)-like plasticity are models of synaptic plasticity which have been associated with memory and learning. The induction of LTD and LTP-like plasticity, using different stimulation protocols, has been proposed as a means of addressing abnormalities in cortical excitability associated with conditions such as focal hand dystonia and stroke. The aim of this study was to investigate whether the excitability of the cortical projections to the tibialis anterior (TA) muscle could be decreased when dorsiflexion of the ankle joint was imagined and paired with peripheral electrical stimulation (ES) of the nerve supplying the antagonist soleus muscle. The effect of stimulus timing was evaluated by comparing paired stimulation timed to reach the cortex before, at and after the onset of imagined movement. Fourteen healthy subjects participated in six experimental sessions held on non-consecutive days. The timing of stimulation delivery was determined offline based on the contingent negative variation (CNV) of electroencephalography brain data obtained during imagined dorsiflexion. Afferent stimulation was provided via a single pulse ES to the peripheral nerve paired, based on the CNV, with motor imagination of ankle dorsiflexion. A significant decrease (P = 0.001) in the excitability of the cortical projection of TA was observed when the afferent volley from the ES of the tibial nerve (TN) reached the cortex at the onset of motor imagination based on the CNV. When TN stimulation was delivered before (P = 0.62), or after (P = 0.23) imagined movement onset there was no significant effect. Nor was a significant effect found when ES of the TN was applied independent of imagined movement (P = 0.45). Therefore, the excitability of the cortical projection to a muscle can be inhibited when ES of the nerve supplying the antagonist muscle is precisely paired with the onset of imagined movement. PMID:26648859

  8. Taurine-induced synaptic potentiation and the late phase of long-term potentiation are related mechanistically.

    PubMed

    del Olmo, N; Handler, A; Alvarez, L; Bustamante, J; Martín del Río, R; Solís, J M

    2003-01-01

    The application of taurine (2-aminoethanesulfonic acid) induces a long-lasting increase of synaptic efficacy and axon excitability (LLP-TAU) in rat hippocampal CA1 area. After taurine withdrawal, LLP-TAU lasted at least 3 h. This fact prompted us to assess whether the mechanisms involved in the maintenance of this particular potentiation were similar to those implicated in the late phase of long-term potentiation (L-LTP). In the presence of KN-62, an inhibitor of calcium/calmodulin-dependent protein kinase, taurine perfusion (10 mM, 30 min) did not affect the induction of LLP-TAU. However, LLP-TAU maintenance was completely suppressed by KT5720, an inhibitor of the cAMP-dependent protein kinase (PKA). Moreover, the late phase of LLP-TAU was blocked by inhibiting protein synthesis with anisomycin. In addition, taurine perfusion increased the phosphorylation of cAMP response element-binding protein (CREB), although did not affect cAMP levels. These features of LLP-TAU do not appear to be caused by the activation of D1/D5 dopamine receptors, as taurine also induced synaptic potentiation in the presence of SCH23390, an antagonist of this type of receptors. Finally, the late phase of both L-LTP and LLP-TAU occluded mutually. These results suggest that taurine triggers the sequence of some of the molecular events involved in the induction of L-LTP.

  9. Long-term Potentiation at Temporoammonic Path-CA1 Synapses in Freely Moving Rats

    PubMed Central

    Gonzalez, Jossina; Villarreal, Desiree M.; Morales, Isaiah S.; Derrick, Brian E.

    2016-01-01

    Hippocampal area CA1 receives direct entorhinal layer III input via the temporoammonic path (TAP) and recent studies implicate TAP-CA1 synapses are important for some aspects of hippocampal memory function. Nonetheless, as few studies have examined TAP-CA1 synaptic plasticity in vivo, the induction and longevity of TAP-CA1 long-term potentiation (LTP) has not been fully characterized. We analyzed CA1 responses following stimulation of the medial aspect of the angular bundle and investigated LTP at medial temporoammonic path (mTAP)-CA1 synapses in freely moving rats. We demonstrate monosynaptic mTAP-CA1 responses can be isolated in vivo as evidenced by observations of independent current sinks in the stratum lacunosum moleculare of both areas CA1 and CA3 following angular bundle stimulation. Contrasting prior indications that TAP input rarely elicits CA1 discharge, we observed mTAP-CA1 responses that appeared to contain putative population spikes in 40% of our behaving animals. Theta burst high frequency stimulation of mTAP afferents resulted in an input specific and N-methyl-D-aspartate (NMDA) receptor-dependent LTP of mTAP-CA1 responses in behaving animals. LTP of mTAP-CA1 responses decayed as a function of two exponential decay curves with time constants (τ) of 2.7 and 148 days to decay 63.2% of maximal LTP. In contrast, mTAP-CA1 population spike potentiation longevity demonstrated a τ of 9.6 days. To our knowledge, these studies provide the first description of mTAP-CA1 LTP longevity in vivo. These data indicate TAP input to area CA1 is a physiologically relevant afferent system that displays robust synaptic plasticity. PMID:26903815

  10. Effects of voluntary exercise on hippocampal long-term potentiation in morphine-dependent rats.

    PubMed

    Miladi-Gorji, H; Rashidy-Pour, A; Fathollahi, Y; Semnanian, S; Jadidi, M

    2014-01-03

    This study was designed to examine the effect of voluntary exercise on hippocampal long-term potentiation (LTP) in morphine-dependent rats. The rats were randomly distributed into the saline-sedentary (Sal/Sed), the dependent-sedentary, the saline-exercise (Sal/Exc), and the dependent-exercise (D/Exc) groups. The Sal/Exc and the D/Exc groups were allowed to freely exercise in a running wheel for 10 days. The Sal/Sed and the morphine-sedentary groups were kept sedentary for the same extent of time. Morphine (10 mg/kg) was injected bi-daily (12 h interval) during 10 days of voluntary exercise. On day 11, 2h after the morphine injection, the in vivo LTP in the dentate gyrus of the hippocampus was examined. The theta frequency primed bursts were delivered to the perforant path for induction of LTP. Population spike (PS) amplitude and the field excitatory post-synaptic potentials (fEPSP) slope were measured as indices of increase in synaptic efficacy. Chronic morphine increased the mean basal EPSP, and augmented PS-LTP. Exercise significantly increased the mean baseline EPSP and PS responses, and augmented PS-LTP in both saline and morphine-treated groups. Moreover, the increase of PS-LTP in the morphine-exercise group was greater (22.5%), but not statistically significant, than that of the Sal/Exc group. These results may imply an additive effect between exercise and morphine on mechanisms of synaptic plasticity. Such an interaction between exercise and chronic morphine may influence cognitive functions in opiate addicts.

  11. Long-term potentiation at spinal C-fiber synapses: a target for pathological pain.

    PubMed

    Liu, Xian-Guo; Zhou, Li-Jun

    2015-01-01

    Long-term potentiation (LTP), referring to a lasting increase in efficacy of synaptic transmission, is a common mechanism of memory storage in central nervous system (CNS). LTP at C-fiber synapses in spinal dorsal horn is considered as a synaptic model of pathological pain, as the spinal LTP is only induced by noxious electrical and natural stimuli but not by innoxious ones and LTPinducible stimulation is capable of leading to lasting behavioral signs of pathological pain in human and in animals. The molecular mechanisms of spinal LTP at C-fiber synapses are similar to hippocampal LTP in following aspects. Induction of LTP depends on postsynaptic Ca(2+) rise resulting from opening of N-methyl-D-aspartate channels (NMDA) and voltage-gated calcium channels (VGCCs), and Ca(2+) release from intracellular store; Early-phase LTP (<3h) needs activation of intracellular protein kinase A (PKA), protein kinase C (PKC), calcium/calmodulin-dependent protein kinase II (CaMKII), phospholipase C (PLC) and release of nitric oxide (NO); Late-phase LTP (>3h) is dependent on de novo protein synthesis; Activation of either dopamine D1 receptors or PKA, and extrogenous brain-derived neurotrophic factor (BDNF) or ATP directly induces late-phase LTP. Therefore, the drugs targeting at the above molecules may impair memory function of hippocampus. The striking difference between hippocampal LTP and spinal LTP at C-fiber synapses is that activation of glial cells and the over-expression of proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin- beta (IL-1β), inhibit LTP in hippocampus, but promote LTP in spinal dorsal horn. The drugs targeting at the neuroinflammatory process may not only attenuate pathological pain but also improve memory in hippocampus.

  12. Stimulus intensity-dependent modulations of hippocampal long-term potentiation by basolateral amygdala priming

    PubMed Central

    Li, Zexuan; Richter-Levin, Gal

    2012-01-01

    There is growing realization that the relationship between memory and stress/emotionality is complicated, and may include both memory enhancing and memory impairing aspects. It has been suggested that the underlying mechanisms involve amygdala modulation of hippocampal synaptic plasticity, such as long-term potentiation (LTP). We recently reported that while in CA1 basolateral amygdala (BLA) priming impaired theta stimulation induced LTP, it enhanced LTP in the dentate gyrus (DG). However, emotional and stressfull experiences were found to activate synaptic plasticity within the BLA, raising the possibility that BLA modulation of other brain regions may be altered as well, as it may depend on the way the BLA is activated or is responding. In previous studies BLA priming stimulation was relatively weak (1 V, 50 μs pulse duration). In the present study we assessed the effects of two stronger levels of BLA priming stimulation (1 V or 2 V, 100 μs pulse duration) on LTP induction in hippocampal DG and CA1, in anesthetized rats. Results show that 1V-BLA priming stimulation enhanced but 2V-BLA priming stimulation impaired DG LTP; however, both levels of BLA priming stimulation impaired CA1 LTP, suggesting that modulation of hippocampal synaptic plasticity by amygdala is dependent on the degree of amygdala activation. These findings suggest that plasticity-induced within the amygdala, by stressful experiences induces a form of metaplasticity that would alter the way the amygdala may modulate memory-related processes in other brain areas, such as the hippocampus. PMID:22586371

  13. Endogenous serotonin facilitates hippocampal long-term potentiation at CA3/CA1 synapses.

    PubMed

    Mlinar, Boris; Stocca, Gabriella; Corradetti, Renato

    2015-02-01

    Encoding of episodic memory requires long-term potentiation (LTP) of neurotransmission at excitatory synapses of the hippocampal circuitry. Previous data obtained with the application of exogenous 5-hydroxytryptamine (5-HT) in hippocampal slices indicate that 5-HT blocks LTP, which contrasts with the facilitatory effect of selective serotonin reuptake inhibitors (SSRIs) on learning and memory observed in vivo. Here, we investigated the effects of endogenous 5-HT, released from terminals by the monoamine releaser 3,4-methylenedioxymethamphetamine (MDMA), on LTP of field EPSPs induced by theta-burst stimulation and recorded at CA3/CA1 synapses of rat hippocampal slices. LTP was greater in the presence of MDMA (10 µM; 45.76 ± 15.75%; n = 28) than in controls (31.26 ± 11.03; n = 21; p < 0.01). This facilitatory effect on LTP persisted when the entry of MDMA in noradrenergic terminals was prevented by the selective noradrenaline reuptake inhibitor nisoxetine (44.90 ± 14.07%; n = 27 vs. 34.49 ± 12.94%; n = 20 in controls; p < 0.05). In both conditions, the facilitation of LTP was abolished by the SSRI citalopram that prevented the entry of MDMA in 5-HT terminals and the subsequent 5-HT release. These data show that, unlike exogenous 5-HT application, release of endogenous 5-HT does not impair cellular mechanisms responsible for induction of LTP, indicating that 5-HT is not detrimental to learning and memory. Moreover, facilitation of LTP by endogenous 5-HT may underlie the in vivo positive effects of augmented 5-HT tone on cognitive performance.

  14. Corticosterone enhances the potency of ethanol against hippocampal long-term potentiation via local neurosteroid synthesis.

    PubMed

    Izumi, Yukitoshi; O'Dell, Kazuko A; Zorumski, Charles F

    2015-01-01

    Corticosterone is known to accumulate in brain after various stressors including alcohol intoxication. Just as severe alcohol intoxication is typically required to impair memory formation only high concentrations of ethanol (60 mM) acutely inhibit long-term potentiation (LTP), a cellular memory mechanism, in naïve hippocampal slices. This LTP inhibition involves synthesis of neurosteroids, including allopregnanolone, and appears to involve a form of cellular stress. In the CA1 region of rat hippocampal slices, we examined whether a lower concentration of ethanol (20 mM) inhibits LTP in the presence of corticosterone, a stress-related modulator, and whether corticosterone stimulates local neurosteroid synthesis. Although low micromolar corticosterone alone did not inhibit LTP induction, we found that 20 mM ethanol inhibited LTP in the presence of corticosterone. At 20 mM, ethanol alone did not stimulate neurosteroid synthesis or inhibit LTP. LTP inhibition by corticosterone plus ethanol was blocked by finasteride, an inhibitor of 5α-reductase, suggesting a role for neurosteroid synthesis. We also found that corticosterone alone enhanced neurosteroid immunostaining in CA1 pyramidal neurons and that this immunostaining was further augmented by 20 mM ethanol. The enhanced neurosteroid staining was blocked by finasteride and the N-methyl-D-aspartate antagonist, 2-amino-5-phosphonovalerate (APV). These results indicate that corticosterone promotes neurosteroid synthesis in hippocampal pyramidal neurons and can participate in ethanol-mediated synaptic dysfunction even at moderate ethanol levels. These effects may contribute to the influence of stress on alcohol-induced cognitive impairment.

  15. Corticosterone enhances the potency of ethanol against hippocampal long-term potentiation via local neurosteroid synthesis

    PubMed Central

    Izumi, Yukitoshi; O’Dell, Kazuko A.; Zorumski, Charles F.

    2015-01-01

    Corticosterone is known to accumulate in brain after various stressors including alcohol intoxication. Just as severe alcohol intoxication is typically required to impair memory formation only high concentrations of ethanol (60 mM) acutely inhibit long-term potentiation (LTP), a cellular memory mechanism, in naïve hippocampal slices. This LTP inhibition involves synthesis of neurosteroids, including allopregnanolone, and appears to involve a form of cellular stress. In the CA1 region of rat hippocampal slices, we examined whether a lower concentration of ethanol (20 mM) inhibits LTP in the presence of corticosterone, a stress-related modulator, and whether corticosterone stimulates local neurosteroid synthesis. Although low micromolar corticosterone alone did not inhibit LTP induction, we found that 20 mM ethanol inhibited LTP in the presence of corticosterone. At 20 mM, ethanol alone did not stimulate neurosteroid synthesis or inhibit LTP. LTP inhibition by corticosterone plus ethanol was blocked by finasteride, an inhibitor of 5α-reductase, suggesting a role for neurosteroid synthesis. We also found that corticosterone alone enhanced neurosteroid immunostaining in CA1 pyramidal neurons and that this immunostaining was further augmented by 20 mM ethanol. The enhanced neurosteroid staining was blocked by finasteride and the N-methyl-D-aspartate antagonist, 2-amino-5-phosphonovalerate (APV). These results indicate that corticosterone promotes neurosteroid synthesis in hippocampal pyramidal neurons and can participate in ethanol-mediated synaptic dysfunction even at moderate ethanol levels. These effects may contribute to the influence of stress on alcohol-induced cognitive impairment. PMID:26190975

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

    PubMed

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

    2010-09-01

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

  17. Effect of the Initial Synaptic State on the Probability to Induce Long-Term Potentiation and Depression

    PubMed Central

    Migliore, Michele; De Simone, Giada; Migliore, Rosanna

    2015-01-01

    Long-term potentiation (LTP) and long-term depression (LTD) are the two major forms of long-lasting synaptic plasticity in the mammalian neurons, and are directly related to higher brain functions such as learning and memory. Experimentally, they are characterized by a change in the strength of a synaptic connection induced by repetitive and properly patterned stimulation protocols. Although many important details of the molecular events leading to LTP and LTD are known, experimenters often report problems in using standard induction protocols to obtain consistent results, especially for LTD in vivo. We hypothesize that a possible source of confusion in interpreting the results, from any given experiment on synaptic plasticity, can be the intrinsic limitation of the experimental techniques, which cannot take into account the actual state and peak conductance of the synapses before the conditioning protocol. In this article, we investigate the possibility that the same experimental protocol may result in different consequences (e.g., LTD instead of LTP), according to the initial conditions of the stimulated synapses, and can generate confusing results. Using biophysical models of synaptic plasticity and hippocampal CA1 pyramidal neurons, we study how, why, and to what extent the phenomena observed at the soma after induction of LTP/LTD reflects the actual (local) synaptic state. The model and the results suggest a physiologically plausible explanation for why LTD induction is experimentally difficult to obtain. They also suggest experimentally testable predictions on the stimulation protocols that may be more effective. PMID:25762316

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

    PubMed

    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.

  19. Long-term Potentiation of Perforant Pathway-dentate Gyrus Synapse in Freely Behaving Mice

    PubMed Central

    Blaise, J. Harry

    2013-01-01

    Studies of long-term potentiation of synaptic efficacy, an activity-dependent synaptic phenomenon having properties that make it attractive as a potential cellular mechanism underlying learning and information storage, have long been used to elucidate the physiology of various neuronal circuits in the hippocampus, amygdala, and other limbic and cortical structures. With this in mind, transgenic mouse models of neurological diseases represent useful platforms to conduct long-term potentiation (LTP) studies to develop a greater understanding of the role of genes in normal and abnormal synaptic communication in neuronal networks involved in learning, emotion and information processing. This article describes methodologies for reliably inducing LTP in the freely behaving mouse. These methodologies can be used in studies of transgenic and knockout freely behaving mouse models of neurodegenerative diseases. PMID:24327052

  20. Long-term potentiation of GABAergic synaptic transmission in neonatal rat hippocampus.

    PubMed

    Caillard, O; Ben-Ari, Y; Gaiarsa, J L

    1999-07-01

    1. The plasticity of GABAergic synapses was investigated in neonatal rat hippocampal slices obtained between postnatal days 3 and 6 using intracellular recording techniques. Ionotropic glutamate receptor antagonists were present throughout the experiments to isolate GABAA receptor-mediated postsynaptic potentials (GABAA PSPs) or currents (GABAA PSCs). 2. Repetitive depolarizing pulses (20 pulses, 0.5 s duration, at 0.1 Hz, each pulse generating 4-6 action potentials) induced a long-term potentiation in the slope and amplitude of the evoked GABAA PSPs and GABAA PSCs. 3. Long-term potentiation was prevented by intracellular injection of the calcium chelator BAPTA (50 mM), or when the voltage-dependent calcium channels blockers Ni2+ (50 microM) and nimodipine (10 microM) were bath applied. 4. Repetitive depolarizing pulses induced a persistent (over 1 h) increase in the frequency of spontaneous GABAA PSCs. 5. Repetitive depolarizing pulses induced a long-lasting increase in the frequency of miniature GABAA PSCs, without altering their amplitude or decay-time constant. 6. It is concluded that the postsynaptic activation of voltage-dependent calcium channels leads to a long-term potentiation of GABAergic synaptic transmission in neonatal rat hippocampus. This form of plasticity is expressed as an increase in the probability of GABA release or in the number of functional synapses, rather than as an upregulation of postsynaptic GABAA receptor numbers or conductance at functional synapses.

  1. CLC-3 chloride channels moderate long-term potentiation at Schaffer collateral–CA1 synapses

    PubMed Central

    Farmer, Laurel M; Le, Brandy N; Nelson, Deborah J

    2013-01-01

    The chloride channel CLC-3 is expressed in the brain on synaptic vesicles and postsynaptic membranes. Although CLC-3 is broadly expressed throughout the brain, the CLC-3 knockout mouse shows complete, selective postnatal neurodegeneration of the hippocampus, suggesting a crucial role for the channel in maintaining normal brain function. CLC-3 channels are functionally linked to NMDA receptors in the hippocampus; NMDA receptor-dependent Ca2+ entry, activation of Ca2+/calmodulin kinase II and subsequent gating of CLC-3 link the channels via a Ca2+-mediated feedback loop. We demonstrate that loss of CLC-3 at mature synapses increases long-term potentiation from 135 ± 4% in the wild-type slice preparation to 154 ± 7% above baseline (P < 0.001) in the knockout; therefore, the contribution of CLC-3 is to reduce synaptic potentiation by ∼40%. Using a decoy peptide representing the Ca2+/calmodulin kinase II phosphorylation site on CLC-3, we show that phosphorylation of CLC-3 is required for its regulatory function in long-term potentiation. CLC-3 is also expressed on synaptic vesicles; however, our data suggest functionally separable pre- and postsynaptic roles. Thus, CLC-3 confers Cl− sensitivity to excitatory synapses, controls the magnitude of long-term potentiation and may provide a protective limit on Ca2+ influx. PMID:23165767

  2. CLC-3 chloride channels moderate long-term potentiation at Schaffer collateral-CA1 synapses.

    PubMed

    Farmer, Laurel M; Le, Brandy N; Nelson, Deborah J

    2013-02-15

    The chloride channel CLC-3 is expressed in the brain on synaptic vesicles and postsynaptic membranes. Although CLC-3 is broadly expressed throughout the brain, the CLC-3 knockout mouse shows complete, selective postnatal neurodegeneration of the hippocampus, suggesting a crucial role for the channel in maintaining normal brain function. CLC-3 channels are functionally linked to NMDA receptors in the hippocampus; NMDA receptor-dependent Ca(2+) entry, activation of Ca(2+)/calmodulin kinase II and subsequent gating of CLC-3 link the channels via a Ca(2+)-mediated feedback loop. We demonstrate that loss of CLC-3 at mature synapses increases long-term potentiation from 135 ± 4% in the wild-type slice preparation to 154 ± 7% above baseline (P < 0.001) in the knockout; therefore, the contribution of CLC-3 is to reduce synaptic potentiation by ∼40%. Using a decoy peptide representing the Ca(2+)/calmodulin kinase II phosphorylation site on CLC-3, we show that phosphorylation of CLC-3 is required for its regulatory function in long-term potentiation. CLC-3 is also expressed on synaptic vesicles; however, our data suggest functionally separable pre- and postsynaptic roles. Thus, CLC-3 confers Cl(-) sensitivity to excitatory synapses, controls the magnitude of long-term potentiation and may provide a protective limit on Ca(2+) influx.

  3. Long-term potentiation in the in vitro perirhinal cortex displays associative properties.

    PubMed

    Bilkey, D K

    1996-09-16

    Brief high frequency tetanization trains reliably induced input-specific long-term potentiation (LTP) in slices of rat perirhinal cortex maintained in vitro. Furthermore, associative interactions between inputs were observed following simultaneous tetanization of separate inputs. This associativity may be mediated via NMDA receptors as LTP was blocked in the presence of APV. These results suggest that LTP may underline participation of perirhinal cortex in memory processes.

  4. Frequency-dependent associative long-term potentiation at the hippocampal mossy fiber-CA3 synapse.

    PubMed

    Derrick, B E; Martinez, J L

    1994-10-25

    The mossy fiber-CA3 synapse displays an N-methyl-D-aspartate-receptor-independent mu-opioid-receptor-dependent form of long-term potentiation (LTP) that is thought not to display cooperativity or associativity with coactive afferents. However, because mossy fiber LTP requires repetitive synaptic activity for its induction, we reevaluated cooperativity and associativity at this synapse by using trains of mossy fiber stimulation. Moderate-, but not low-, intensity trains induced mossy fiber LTP, indicating cooperativity. Low-intensity mossy fiber trains that were normally ineffective in inducing LTP could induce mossy fiber LTP when delivered in conjunction with trains delivered to commissural-CA3 afferents. Associative mossy fiber LTP also could be induced with single mossy fiber pulses when delivered with commissural trains in the presence of a mu-opioid-receptor agonist. Our findings suggest a frequency-dependent variation of Hebbian associative LTP induction that is regulated by the release of endogenous opioid peptides.

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

    EPA Science Inventory

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

  6. Long-term CO2 Reduction Potential by Promoting Electric Technologies

    NASA Astrophysics Data System (ADS)

    Nishio, Ken-Ichiro

    This article reviews past studies on the long-term CO2 abatement strategy dealing with electric technologies and thereby attempts to draw sound understandings of effectiveness of those measures. It is widely known that electrification of final energy uses plays an important role to mitigate CO2 emissions through curbing fossil fuel consumption. Electrification of thermal demand by high-efficient heat-pump technologies is considered as a realistic example, while electric vehicles including plug-in hybrid vehicles are getting higher expectations as an alternative in the transportation sector. It is of crucial importance, therefore, to carefully analyze the potential of CO2 emission reductions by these measures and to establish viable long-term strategies taking them fully into consideration. The author provides a numerical representation of such strategy development up to the year 2050.

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

    PubMed

    Izquierdo, Iván; Cammarota, Martín; Da Silva, Weber C; Bevilaqua, Lia R M; Rossato, Janine I; Bonini, Juliana S; Mello, Pamela; Benetti, Fernando; Costa, Jaderson C; Medina, Jorge H

    2008-03-01

    Long-term potentiation (LTP) is the enhancement of postsynaptic responses for hours, days or weeks following the brief repetitive afferent stimulation of presynaptic afferents. It has been proposed many times over the last 30 years to be the basis of long-term memory. Several recent findings finally supported this hypothesis: a) memory formation of one-trial avoidance learning depends on a series of molecular steps in the CA1 region of the hippocampus almost identical to those of LTP in the same region; b)hippocampal LTP in this region accompanies memory formation of that task and of another similar task. However, CA1 LTP and the accompanying memory processes can be dissociated, and in addition plastic events in several other brain regions(amygdala, entorhinal cortex, parietal cortex) are also necessary for memory formation of the one-trial task, and perhaps of many others.

  8. Nitric oxide-dependent long-term depression but not endocannabinoid-mediated long-term potentiation is crucial for visual recognition memory

    PubMed Central

    Tamagnini, Francesco; Barker, Gareth; Warburton, E Clea; Burattini, Costanza; Aicardi, Giorgio; Bashir, Zafar I

    2013-01-01

    Synaptic plasticity in perirhinal cortex is essential for recognition memory. Nitric oxide and endocannabinoids (eCBs), which are produced in the postsynaptic cell and act on the presynaptic terminal, are implicated in mechanisms of long-term potentiation (LTP) and long-term depression (LTD) in other brain regions. In this study, we examine these two retrograde signalling cascades in perirhinal cortex synaptic plasticity and in visual recognition memory in the rat. We show that inhibition of NO-dependent signalling prevented both carbachol- and activity (5 Hz)-dependent LTD but not activity (100 Hz theta burst)-dependent LTP in the rat perirhinal cortex in vitro. In contrast, inhibition of the eCB-dependent signalling prevented LTP but not the two forms of LTD in vitro. Local administration into perirhinal cortex of the nitric oxide synthase inhibitor NPA (2 μm) disrupted acquisition of long-term visual recognition memory. In contrast, AM251 (10 μm), a cannabinoid receptor 1 antagonist, did not impair visual recognition memory. The results of this study demonstrate dissociation between putative retrograde signalling mechanisms in LTD and LTP in perirhinal cortex. Thus, LTP relies on cannabinoid but not NO signalling, whilst LTD relies on NO- but not eCB-dependent signalling. Critically, these results also establish, for the first time, that NO- but not eCB-dependent signalling is important in perirhinal cortex-dependent visual recognition memory. PMID:23671159

  9. Improving potato drought tolerance through the induction of long-term water stress memory.

    PubMed

    Ramírez, D A; Rolando, J L; Yactayo, W; Monneveux, P; Mares, V; Quiroz, R

    2015-09-01

    Knowledge of drought tolerance in potato is limited and very little is known about stress memory in this crop. In the present study, long-term stress memory was tested on tuber yield and drought tolerance related traits in three potato varieties (Unica, Désirée and Sarnav) with contrasted yields under water restriction. Seed tubers produced by plants grown under non-restricted (non-primed tubers) and restricted (primed tubers) water conditions were sown and exposed to similar watering treatments. Tuber yield and leaf greenness of plants from primed and non-primed seeds as well as tuber carbon isotope discrimination (Δ(13)C) and antioxidant activity (AA) responses to watering treatments were compared. Higher tuber yield, both under non-restricted and restricted water regimes, was produced by primed Sarnav plants. The decrease of tuber yield and Δ(13)C with water restriction was lower in primed Unica plants. Long-term stress memory consequently appears to be highly genotype-dependent in potato. Its expression in plants originated from primed tubers and facing water restriction seems to be positively associated to the degree of inherent capability of the cultivar to yield under water restriction. However, other effects of priming appear to be genotype-independent as priming enhanced the tuber AA in response to water restriction in the three varieties.

  10. Mechanisms of induction and expression of long-term depression at GABAergic synapses in the neonatal rat hippocampus.

    PubMed

    Caillard, O; Ben-Ari, Y; Gaïarsa, J L

    1999-09-01

    Synaptic plasticity at excitatory glutamatergic synapses is believed to be instrumental in the maturation of neuronal networks. Using whole-cell patch-clamp recordings, we have studied the mechanisms of induction and expression of long-term depression at excitatory GABAergic synapses in the neonatal rat hippocampus (LTD(GABA-A)). We report that the induction of LTD(GABA-A) requires a GABA(A) receptor-mediated membrane depolarization, which is necessary to remove the Mg(2+) block from postsynaptic NMDA receptors. LTD(GABA-A) is associated with an increase in the coefficient of variation of evoked GABA(A) receptor-mediated synaptic currents and a decrease in the frequency, but not amplitude, of Sr(2+)-induced asynchronous GABA(A) quantal events. We conclude that LTD(GABA-A) induction requires the activation of both GABA(A) and NMDA postsynaptic receptors and that its expression is likely presynaptic.

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

    PubMed Central

    Rancourt, Carol; Moisan, Jocelyne; Baillargeon, Lucie; Verreault, René; Laurin, Danielle; Grégoire, Jean-Pierre

    2004-01-01

    Background Inappropriate medication use is a major healthcare issue for the elderly population. This study explored the prevalence of potentially inappropriate prescriptions (PIPs) in long-term care in metropolitan Quebec. Methods A cross sectional chart review of 2,633 long-term care older patients of the Quebec City area was performed. An explicit criteria list for PIPs was developed based on the literature and validated by a modified Delphi method. Medication orders were reviewed to describe prescribing patterns and to determine the prevalence of PIPs. A multivariate analysis was performed to identify predictors of PIPs. Results Almost all residents (94.0%) were receiving one or more prescribed medication; on average patients had 4.8 prescribed medications. A majority (54.7%) of treated patients had a potentially inappropriate prescription (PIP). Most common PIPs were drug interactions (33.9% of treated patients), followed by potentially inappropriate duration (23.6%), potentially inappropriate medication (14.7%) and potentially inappropriate dosage (9.6%). PIPs were most frequent for medications of the central nervous system (10.8% of prescribed medication). The likelihood of PIP increased significantly as the number of drugs prescribed increased (odds ratio [OR]: 1.38, 95% confidence interval [CI]: 1.33 – 1.43) and with the length of stay (OR: 1.78, CI: 1.43 – 2.20). On the other hand, the risk of receiving a PIP decreased with age. Conclusion Potentially inappropriate prescribing is a serious problem in the highly medicated long-term care population in metropolitan Quebec. Use of explicit criteria lists may help identify the most critical issues and prioritize interventions to improve quality of care and patient safety. PMID:15488143

  12. A ketogenic diet reduces long-term potentiation in the dentate gyrus of freely behaving rats.

    PubMed

    Koranda, Jessica L; Ruskin, David N; Masino, Susan A; Blaise, J Harry

    2011-08-01

    Ketogenic diets are very low in carbohydrates and can reduce epileptic seizures significantly. This dietary therapy is particularly effective in pediatric and drug-resistant epilepsy. Hypothesized anticonvulsant mechanisms of ketogenic diets focus on increased inhibition and/or decreased excitability/excitation. Either of these consequences might not only reduce seizures, but also could affect normal brain function and synaptic plasticity. Here, we characterized effects of a ketogenic diet on hippocampal long-term potentiation, a widely studied form of synaptic plasticity. Adult male rats were placed on a control or ketogenic diet for 3 wk before recording. To maintain the most physiological conditions possible, we assessed synaptic transmission and plasticity using chronic in vivo recordings in freely behaving animals. Rats underwent stereotaxic surgery to chronically implant a recording electrode in the hippocampal dentate gyrus and a stimulating electrode in the perforant path; they recovered for 1 wk. After habituation and stable baseline recording, 5-Hz theta-burst stimulation was delivered to induce long-term potentiation. All animals showed successful plasticity, demonstrating that potentiation was not blocked by the ketogenic diet. Compared with rats fed a control diet, rats fed a ketogenic diet demonstrated significantly diminished long-term potentiation. This decreased potentiation lasted for at least 48 h. Reduced potentiation in ketogenic diet-fed rats is consistent with a general increase in neuronal inhibition (or decrease in excitability) and decreased seizure susceptibility. A better understanding of the effects of ketogenic diets on synaptic plasticity and learning is important, as diet-based therapy is often prescribed to children with epilepsy.

  13. DHHC8-dependent PICK1 palmitoylation is required for induction of cerebellar long-term synaptic depression.

    PubMed

    Thomas, Gareth M; Hayashi, Takashi; Huganir, Richard L; Linden, David J

    2013-09-25

    The palmitoyl acyltransferase (PAT) DHHC8 is implicated in synaptic regulation but few DHHC8 substrates are known. Here we report that DHHC8 binds and palmitoylates the PDZ domain-containing protein PICK1 at a cysteine residue that is essential for long-term synaptic depression (LTD) in cultured mouse cerebellar Purkinje neurons. Cerebellar LTD is palmitoylation-dependent and induction of LTD requires DHHC8. Furthermore, PICK1 is a critical DHHC8 substrate whose palmitoylation is necessary for LTD. These results identify the first DHHC8 substrate required for a specific form of synaptic plasticity and provide new insights into synaptic roles of palmitoylation.

  14. Running enhances neurogenesis, learning, and long-term potentiation in mice

    PubMed Central

    van Praag, Henriette; Christie, Brian R.; Sejnowski, Terrence J.; Gage, Fred H.

    1999-01-01

    Running increases neurogenesis in the dentate gyrus of the hippocampus, a brain structure that is important for memory function. Consequently, spatial learning and long-term potentiation (LTP) were tested in groups of mice housed either with a running wheel (runners) or under standard conditions (controls). Mice were injected with bromodeoxyuridine to label dividing cells and trained in the Morris water maze. LTP was studied in the dentate gyrus and area CA1 in hippocampal slices from these mice. Running improved water maze performance, increased bromodeoxyuridine-positive cell numbers, and selectively enhanced dentate gyrus LTP. Our results indicate that physical activity can regulate hippocampal neurogenesis, synaptic plasticity, and learning. PMID:10557337

  15. Hyperammonemia impairs NMDA receptor-dependent long-term potentiation in the CA1 of rat hippocampus in vitro.

    PubMed

    Muñoz, M D; Monfort, P; Gaztelu, J M; Felipo, V

    2000-04-01

    Hyperammonemia is considered the main factor responsible for the neurological and cognitive alterations found in hepatic encephalopathy and in patients with congenital deficiencies of the urea cycle enzymes. The underlying mechanisms remain unclear. Chronic moderate hyperammonemia reduces nitric oxide-induced activation of soluble guanylate cyclase and glutamate-induced formation of cGMP. NMDA receptor-associated transduction pathways, including activation of soluble guanylate cyclase, are involved in the induction of long-term potentiation (LTP), a phenomenon that is considered to be the molecular basis for some forms of memory and learning. Using an animal model we show that chronic hyperammonemia significantly reduces the degree of long-term potentiation induced in the CA1 of hippocampus slices (200% increase in control and 50% increase in slices of hyperammonemic animals). Also, addition of 1 mM ammonia impaired the maintenance of non-decremental LTP. The LTP impairment could be involved in the intellectual impairment present in chronic hepatocerebral disorders associated with hyperammonemia.

  16. Effects of selenium treatment on 6-n-propyl-2-thiouracil-induced impairment of long-term potentiation.

    PubMed

    Bitiktaş, Soner; Tan, Burak; Batakçı, Melek; Kavraal, Şehrazat; Dursun, Nurcan; Süer, Cem

    2016-08-01

    The goal of this study was to evaluate whether sodium selenite could afford protection against the effects of hypothyroidism on long-term potentiation (LTP), which is thought to be the cellular basis for learning and memory. Hypothyroidism was induced in young-adult rats by the administration of 6-n-propyl-2-thiouracil (PTU) in tap water for 21 days. Half of these hypothyroid and euthroid rats were given 10ppM selenium with their drinking water. Field potentials were recorded from the dentate gyrus in response to stimulation of the medial perforant pathway in vivo. PTU treatment resulted in a significant reduction in both free T3 and free T4 levels, whereas selenium administration to PTU-treated rats restored only the levels of free T3 to their control values. Thyroid hormone levels were not affected by selenium in euthyroid rats. PTU-treated rats exhibited an attenuation of population spike (PS) - LTP, but a comparable potentiation of excitatory postsynaptic potential (EPSP) was found among these rats. The administration of selenium to PTU-treated rats was partially able to attenuate impairment of LTP, but not of potentiation during the LTP induction protocol in hypothyroid rats. Interestingly, the hypothyroid rats that were supplemented with selenium had a lower EPSP potentiation during induction protocol than the control rats. The present study suggests a possible importance of T3 in Se-induced rescue of impaired PS-LTP in hypothyroidism.

  17. Induction of metallothionein synthesis with preservation of testicular function in rats following long term renal transplantation.

    PubMed

    Cai, L; Deng, D X; Jiang, J; Chen, S; Zhong, R; Cherian, M G; Chakrabarti, S

    2000-04-01

    Metallothionein (MT), as an acute phase or stress-response protein and free radical scavenger, is related to inflammation and cellular protection from oxidative damage. In order to evaluate long-term testicular damage and the role of MT following renal transplant, nine allogenic (Fisher 344 --> Lewis) and seven isogenic (Lewis --> Lewis) renal transplants were performed and the recipient rats were followed for 140 days when allografts develop chronic transplant rejection. Testicular weight, light microscopic morphology, and lactate dehydrogenase-X enzyme activity were assessed. Testicular MT was determined by Cd-heme assay, and was localized immunocytochemically using a polyclonal rabbit antibody. No differences in testis weight, morphology, or LDH-X enzyme activity were found between allograft and isograft recipients. Testicular MT level was significantly increased in the testis of allograft recipients. Testicular zinc (Zn) and copper (Cu) levels, but not iron (Fe) level, were significantly higher in testis with allograft kidney than that with isograft kidney. In addition, Cu/Zn ratio was also significantly high in the allograft group. However, the MT level did not show any significant correlation either with Cu and Zn alone or with Cu/Zn and Fe/Zn ratios. These data suggest that allogenic stimuli may induce MT synthesis in the recipient testis. The increased MT level in an allograft may offer a protective action from oxidative damage in the testis.

  18. Reward improves long-term retention of a motor memory through induction of offline memory gains

    PubMed Central

    Abe, Mitsunari; Schambra, Heidi; Wassermann, Eric M; Luckenbaugh, Dave; Schweighofer, Nicolas; Cohen, Leonardo G

    2011-01-01

    Summary In humans, training in which good performance is rewarded or bad performance punished results in transient behavioral improvements [1–3]. Their relative effects on consolidation and long-term retention, critical behavioral stages for successful learning [4, 5], are not known. Here, we investigated the effects of reward and punishment on these different stages of human motor skill learning. We studied healthy subjects who trained on a motor task under rewarded, punished, or neutral control conditions. Performance was tested before, and immediately, 6 hs, 24 hs and 30 days after training in the absence of reward or punishment. Performance improvements immediately after training were comparable in the three groups. At 6 hs, the rewarded group maintained performance gains while the other two groups experienced significant forgetting. At 24 hs, the reward group showed significant offline (posttraining) improvements while the other two groups did not. At 30 days, the rewarded group retained the gains identified at 24 hs, while the other two groups experienced significant forgetting. We conclude that training under rewarded conditions is more effective than training under punished or neutral conditions in eliciting lasting motor learning, an advantage driven by offline memory gains that persist over time. PMID:21419628

  19. Potential of mass trapping for long-term pest management and eradication of invasive species.

    PubMed

    El-Sayed, A M; Suckling, D M; Wearing, C H; Byers, J A

    2006-10-01

    Semiochemical-based pest management programs comprise three major approaches that are being used to provide environmentally friendly control methods of insect pests: mass trapping, "lure and kill," and mating disruption. In this article, we review the potential of mass trapping in long-term pest management as well as in the eradication of invasive species. We discuss similarities and differences between mass trapping and other two main approaches of semiochemical-based pest management programs. We highlight several study cases where mass trapping has been used either in long-term pest management [e.g., codling moth, Cydia pomonella (L.); pink bollworm, Pectinophora gossypiella (Saunders); bark beetles, palm weevils, corn rootworms (Diabrotica spp.); and fruit flies] or in eradication of invasive species [e.g., gypsy moth, Lymantria dispar (L.); and boll weevil, Anthonomus grandis grandis Boheman). We list the critical issues that affect the efficacy of mass trapping and compare these with previously published models developed to investigate mass trapping efficacy in pest control. We conclude that mass trapping has good potential to suppress or eradicate low-density, isolated pest populations; however, its full potential in pest management has not been adequately realized and therefore encourages further research and development of this technology.

  20. Ethanol inhibits long-term potentiation in hippocampal CA1 neurons, irrespective of lamina and stimulus strength, through neurosteroidogenesis.

    PubMed

    Ramachandran, Binu; Ahmed, Saheeb; Zafar, Noman; Dean, Camin

    2015-01-01

    Ethanol inhibits memory encoding and the induction of long-term potentiation (LTP) in CA1 neurons of the hippocampus. Hippocampal LTP at Schaffer collateral synapses onto CA1 pyramidal neurons has been widely studied as a cellular model of learning and memory, but there is striking heterogeneity in the underlying molecular mechanisms in distinct regions and in response to distinct stimuli. Basal and apical dendrites differ in terms of innervation, input specificity, and molecular mechanisms of LTP induction and maintenance, and different stimuli determine distinct molecular pathways of potentiation. However, lamina or stimulus-dependent effects of ethanol on LTP have not been investigated. Here, we tested the effect of acute application of 60 mM ethanol on LTP induction in distinct dendritic compartments (apical versus basal) of CA1 neurons, and in response to distinct stimulation paradigms (single versus repeated, spaced high frequency stimulation). We found that ethanol completely blocks LTP in apical dendrites, whereas it reduces the magnitude of LTP in basal dendrites. Acute ethanol treatment for just 15 min altered pre- and post-synaptic protein expression. Interestingly, ethanol increases the neurosteroid allopregnanolone, which causes ethanol-dependent inhibition of LTP, more prominently in apical dendrites, where ethanol has greater effects on LTP. This suggests that ethanol has general effects on fundamental properties of synaptic plasticity, but the magnitude of its effect on LTP differs depending on hippocampal sub-region and stimulus strength.

  1. Long-term changes in pigmentation of arctic Daphnia provide potential for reconstructing aquatic UV exposure

    NASA Astrophysics Data System (ADS)

    Nevalainen, Liisa; Rantala, Marttiina V.; Luoto, Tomi P.; Ojala, Antti E. K.; Rautio, Milla

    2016-07-01

    Despite the biologically damaging impacts of solar ultraviolet radiation (UV) in nature, little is known about its natural variability, forcing mechanisms, and long-term effects on ecosystems and organisms. Arctic zooplankton, for example the aquatic keystone genus Daphnia (Crustacea, Cladocera) responds to biologically damaging UV by utilizing photoprotective strategies, including pigmentation. We examined the preservation and content of UV-screening pigments in fossil Daphnia remains (ephippia) in two arctic lake sediment cores from Cornwallis Island (Lake R1), Canada, and Spitsbergen (Lake Fugledammen), Svalbard. The aims were to document changes in the degree of UV-protective pigmentation throughout the past centuries, elucidate the adaptive responses of zooplankton to long-term variations in UV exposure, and estimate the potential of fossil zooplankton pigments in reconstructing aquatic UV regimes. The spectroscopic absorbance measurements of fossil Daphnia ephippia under UV (280-400 nm) and visible light (400-700 nm) spectral ranges indicated that melanin (absorbance maxima at UV wavebands 280-350 nm) and carotenoids (absorbance maxima at 400-450 nm) pigments were preserved in the ephippia in both sediment cores. Downcore measurements of the most important UV-protective pigment melanin (absorbance measured at 305 and 340 nm) showed marked long-term variations in the degree of melanisation. These variations likely represented long-term trends in aquatic UV exposure and were positively related with solar radiation intensity. The corresponding trends in melanisation and solar activity were disrupted at the turn of the 20th century in R1, but remained as strong in Fugledammen. The reversed trends in the R1 core were simultaneous with a significant aquatic community reorganization taking place in the lake, suggesting that recent environmental changes, likely related to climate warming had a local effect on pigmentation strategies. This time horizon is also

  2. Inhibitory long-term potentiation underlies auditory conditioning of goldfish escape behaviour.

    PubMed

    Oda, Y; Kawasaki, K; Morita, M; Korn, H; Matsui, H

    1998-07-09

    Long-term potentiation (LTP), the increase in synaptic strength evoked by high-frequency stimulation, is often considered to be a cellular model for learning and memory. The validity of this model depends on the assumptions that physiological stimuli can induce LTP in vivo and that the resulting synaptic modifications correlate with behavioural changes. However, modifiable synapses are generally embedded deep in complex circuits. In contrast, the goldfish Mauthner (M)-cell and its afferent synapses are easily accessible for electrophysiological studies, and firing of this neuron is sufficient to trigger fast escape behaviour in response to sudden stimuli. We have previously shown that tetanic stimulation can induce LTP of the feedforward inhibitory synapses that control the excitability of the M-cell. Here we report that natural sensory stimulation can induce potentiation of this inhibitory connection that resembles the LTP induced by afferent tetanization. Furthermore, comparable acoustic stimulation produced a parallel decrease in the probability of the sound-evoked escape reflex. Thus we demonstrate for the first time, to our knowledge, a behavioural role for the long-term synaptic strengthening of inhibitory synapses.

  3. The age-related attenuation in long-term potentiation is associated with microglial activation.

    PubMed

    Griffin, Rebecca; Nally, Rachel; Nolan, Yvonne; McCartney, Yvonne; Linden, James; Lynch, Marina A

    2006-11-01

    It is well established that inflammatory changes contribute to brain ageing, and an increased concentration of proinflammatory cytokine, interleukin-1beta (IL-1beta), has been reported in the aged brain associated with a deficit in long-term potentiation (LTP) in rat hippocampus. The precise age at which changes are initiated is unclear. In this study, we investigate parallel changes in markers of inflammation and LTP in 3-, 9- and 15-month-old rats. We report evidence of increased hippocampal concentrations of the proinflammatory cytokines IL-1alpha, IL-18 and interferon-gamma (IFNgamma), which are accompanied by deficits in LTP in the older rats. We also show an increase in expression of markers of microglial activation, CD86, CD40 and intercellular adhesion molecules (ICAM). Associated with these changes, we observed a significant impairment of hippocampal LTP in the same rats. The importance of microglial activation in the attenuation of long-term potentiation (LTP) was demonstrated using an inhibitor of microglial activation, minocycline; partial restoration of LTP in 15-month-old rats was observed following administration of minocycline. We propose that signs of neuroinflammation are observed in middle age and that these changes, which are characterized by microglial activation, may be triggered by IL-18.

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

    NASA Astrophysics Data System (ADS)

    Ordikhani, F.; Simchi, A.

    2014-10-01

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

  5. Wip1 phosphatase modulates both long-term potentiation and long-term depression through the dephosphorylation of CaMKII.

    PubMed

    He, Zhi-Yong; Hu, Wei-Yan; Zhang, Ming; Yang, Zara Zhuyun; Zhu, Hong-Mei; Xing, Da; Ma, Quan-Hong; Xiao, Zhi-Cheng

    2016-05-03

    Synaptic plasticity is an important mechanism that underlies learning and cognition. Protein phosphorylation by kinases and dephosphorylation by phosphatases play critical roles in the activity-dependent alteration of synaptic plasticity. In this study, we report that Wip1, a protein phosphatase, is essential for long-term potentiation (LTP) and long-term depression (LTD) processes. Wip1-deletion suppresses LTP and enhances LTD in the hippocampus CA1 area. Wip1 deficiency-induced aberrant elevation of CaMKII T286/287 and T305 phosphorylation underlies these dysfunctions. Moreover, we showed that Wip1 modulates CaMKII dephosphorylation. Wip1(-/-) mice exhibit abnormal GluR1 membrane expression, which could be reversed by the application of a CaMKII inhibitor, indicating that Wip1/CaMKII signaling is crucial for synaptic plasticity. Together, our results demonstrate that Wip1 phosphatase plays a vital role in regulating hippocampal synaptic plasticity by modulating the phosphorylation of CaMKII.

  6. Coincident Activity of Converging Pathways Enables Simultaneous Long-Term Potentiation and Long-Term Depression in Hippocampal CA1 Network In Vivo

    PubMed Central

    Cao, Jun; Zhang, Xia; Xu, Lin

    2008-01-01

    Memory is believed to depend on activity-dependent changes in the strength of synapses, e.g. long-term potentiation (LTP) and long-term depression (LTD), which can be determined by the sequence of coincident pre- and postsynaptic activity, respectively. It remains unclear, however, whether and how coincident activity of converging efferent pathways can enable LTP and LTD in the pathways simultaneously. Here, we report that, in pentobarbital-anesthetized rats, stimulation (600 pulses, 5 Hz) to Schaffer preceding to commissural pathway within a 40-ms timing window induced similar magnitudes of LTP in both pathways onto synapses of CA1 neurons, with varied LTP magnitudes after reversal of the stimulation sequence. In contrast, in urethane-anesthetized or freely-moving rats, the stimulation to Schaffer preceding to commissural pathway induced Schaffer LTP and commissural LTD simultaneously within a 40-ms timing window, without affecting synaptic efficacy in the reversed stimulation sequence. Coincident activity of Schaffer pathways confirmed the above findings under pentobarbital and urethane anesthesia. Thus, coincident activity of converging afferent pathways tends to switch the pathways to be LTP only or LTP/LTD depending on the activity states of the hippocampus. This network rule strengthens the view that activity-dependent synaptic plasticity may well contribute to memory process of the hippocampal network with flexibility or stability from one state to another. PMID:18682723

  7. Acute pentobarbital treatment impairs spatial learning and memory and hippocampal long-term potentiation in rats.

    PubMed

    Wang, Wei; Tan, Tao; Tu, Man; He, Wenting; Dong, Zhifang; Han, Huili

    2015-10-01

    Reports of the effects of pentobarbital on learning and memory are contradictory. Some studies have not shown any interference with learning and memory, whereas others have shown that pentobarbital impairs memory and that these impairments can last for long periods. However, it is unclear whether acute local microinjections of pentobarbital affect learning and memory, and if so, the potential mechanisms are also unclear. Here, we reported that the intra-hippocampal infusion of pentobarbital (8.0mM, 1μl per side) significantly impaired hippocampus-dependent spatial learning and memory retrieval. Moreover, in vitro electrophysiological recordings revealed that these behavioral changes were accompanied by impaired hippocampal CA1 long-term potentiation (LTP) and suppressed neuronal excitability as reflected by a decrease in the number of action potentials (APs). These results suggest that acute pentobarbital application causes spatial learning and memory deficits that might be attributable to the suppression of synaptic plasticity and neuronal excitability.

  8. Dendritic sodium spikes are required for long-term potentiation at distal synapses on hippocampal pyramidal neurons

    PubMed Central

    Kim, Yujin; Hsu, Ching-Lung; Cembrowski, Mark S; Mensh, Brett D; Spruston, Nelson

    2015-01-01

    Dendritic integration of synaptic inputs mediates rapid neural computation as well as longer-lasting plasticity. Several channel types can mediate dendritically initiated spikes (dSpikes), which may impact information processing and storage across multiple timescales; however, the roles of different channels in the rapid vs long-term effects of dSpikes are unknown. We show here that dSpikes mediated by Nav channels (blocked by a low concentration of TTX) are required for long-term potentiation (LTP) in the distal apical dendrites of hippocampal pyramidal neurons. Furthermore, imaging, simulations, and buffering experiments all support a model whereby fast Nav channel-mediated dSpikes (Na-dSpikes) contribute to LTP induction by promoting large, transient, localized increases in intracellular calcium concentration near the calcium-conducting pores of NMDAR and L-type Cav channels. Thus, in addition to contributing to rapid neural processing, Na-dSpikes are likely to contribute to memory formation via their role in long-lasting synaptic plasticity. DOI: http://dx.doi.org/10.7554/eLife.06414.001 PMID:26247712

  9. Long-Term Potentiation by Theta-Burst Stimulation Using Extracellular Field Potential Recordings in Acute Hippocampal Slices.

    PubMed

    Abrahamsson, Therese; Lalanne, Txomin; Watt, Alanna J; Sjöström, P Jesper

    2016-06-01

    This protocol describes how to carry out theta-burst long-term potentiation (LTP) with extracellular field recordings in acute rodent hippocampal slices. This method is relatively simple and noninvasive and provides a way to sample many neurons simultaneously, making it suitable for applications requiring higher throughput than whole-cell recording.

  10. Long-Term Potentiation by Theta-Burst Stimulation using Extracellular Field Potential Recordings in Acute Hippocampal Slices

    PubMed Central

    Abrahamsson, Therese; Lalanne, Txomin; Watt, Alanna J.; Sjöström, P. Jesper

    2017-01-01

    This protocol describes how to carry out theta-burst long-term potentiation (LTP) with extracellular field recordings in acute rodent hippocampal slices. This method is relatively simple and noninvasive and provides a way to sample many neurons simultaneously, making it suitable for applications requiring higher throughput than whole-cell recording. PMID:27250947

  11. A model of the mechanism of cooperativity and associativity of long-term potentiation in the hippocampus: a fundamental mechanism of associative memory and learning.

    PubMed

    Kitajima, T; Hara, K

    1991-01-01

    Long-Term Potentiation (LTP) has three properties: (1) input specificity, (2) cooperativity and (3) associativity. In a previous paper, we proposed an integrated model of the mechanisms of the induction and maintenance of LTP with input specificity. In this paper, a model of the mechanism of cooperative and associative LTP is described. According to computer simulations of the model, its mechanism is based on the spread of synaptic potentials.

  12. Long-term effect of heme oxygenase (HO)-1 induction in glomerular immune injury.

    PubMed

    Datta, Prasun K; Duann, Pu; Lianos, Elias A

    2006-03-01

    In a rat model of macrophage-dependent glomerular immune injury induced by administration of antibody against the glomerular basement membrane (anti-GBM), the authors assessed the anti-proteinuric effect of Heme Oxygenase-1 (HO-1) induction. Rats received anti-GBM antibody alone, anti-GBM antibody and treatment with the HO-1 inducer, hemin, or non-immune serum (controls). Urine protein, creatinine, and nitrite/nitrate excretion were measured on days 5, 7, and 14 after administration of the anti-GBM antibody. In hemin-treated animals with anti-GBM antibody-induced immune injury, HO-1 immunolocalized in macrophages infiltrating glomeruli and in tubular epithelial cells. In these animals, proteinuria was decreased. There was also a decrease in blood urea nitrogen (BUN) levels without a change in serum creatinine or systemic blood pressure. The observations establish the anti-proteinuric effect of hemin induction. This effect could be mechanistically linked to blunting of the ability of infiltrating macrophages to cause injury or to changes in tubular handling of filtered protein.

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

    PubMed Central

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

    2014-01-01

    Ampakines are allosteric modulators of AMPA receptors that facilitate hippocampal long-term potentiation (LTP) and learning, and have been considered for the treatment of cognition and memory deficits. Here, we show that the ampakine CX546 raises the amplitude and slows the decay time of excitatory postsynaptic currents (EPSCs) at cerebellar parallel fiber (PF) to Purkinje cell synapses, thus resembling CX546 effects described at hippocampal synapses. Using the fluorescent calcium indicator dye Oregon Green BAPTA-2 and an ultra-high-speed CCD camera, we also monitored calcium transients in Purkinje cell dendrites. In the presence of CX546 in the bath, PF-evoked calcium transients were enhanced and prolonged, suggesting that CX546 not only enhances synaptic transmission, but also boosts dendritic calcium signaling at cerebellar synapses. In contrast to previous observations in the hippocampus, however, CX546 applied during cerebellar recordings facilitates long-term depression (LTD) rather than LTP at PF synapses. These findings show that ampakines selectively modify the LTP–LTD balance depending on the brain area and type of synapse, and may provide tools for the targeted regulation of synaptic memories. PMID:25403454

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

    PubMed

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

    2014-12-01

    Ampakines are allosteric modulators of AMPA receptors that facilitate hippocampal long-term potentiation (LTP) and learning, and have been considered for the treatment of cognition and memory deficits. Here, we show that the ampakine CX546 raises the amplitude and slows the decay time of excitatory postsynaptic currents (EPSCs) at cerebellar parallel fiber (PF) to Purkinje cell synapses, thus resembling CX546 effects described at hippocampal synapses. Using the fluorescent calcium indicator dye Oregon Green BAPTA-2 and an ultra-high-speed CCD camera, we also monitored calcium transients in Purkinje cell dendrites. In the presence of CX546 in the bath, PF-evoked calcium transients were enhanced and prolonged, suggesting that CX546 not only enhances synaptic transmission, but also boosts dendritic calcium signaling at cerebellar synapses. In contrast to previous observations in the hippocampus, however, CX546 applied during cerebellar recordings facilitates long-term depression (LTD) rather than LTP at PF synapses. These findings show that ampakines selectively modify the LTP-LTD balance depending on the brain area and type of synapse, and may provide tools for the targeted regulation of synaptic memories.

  15. Role of ionotropic glutamate receptors in long-term potentiation in rat hippocampal CA1 oriens-lacunosum moleculare interneurons.

    PubMed

    Oren, Iris; Nissen, Wiebke; Kullmann, Dimitri M; Somogyi, Peter; Lamsa, Karri P

    2009-01-28

    Some interneurons of the hippocampus exhibit NMDA receptor-independent long-term potentiation (LTP) that is induced by presynaptic glutamate release when the postsynaptic membrane potential is hyperpolarized. This "anti-Hebbian" form of LTP is prevented by postsynaptic depolarization or by blocking AMPA and kainate receptors. Although both AMPA and kainate receptors are expressed in hippocampal interneurons, their relative roles in anti-Hebbian LTP are not known. Because interneuron diversity potentially conceals simple rules underlying different forms of plasticity, we focus on glutamatergic synapses onto a subset of interneurons with dendrites in stratum oriens and a main ascending axon that projects to stratum lacunosum moleculare, the oriens-lacunosum moleculare (O-LM) cells. We show that anti-Hebbian LTP in O-LM interneurons has consistent induction and expression properties, and is prevented by selective inhibition of AMPA receptors. The majority of the ionotropic glutamatergic synaptic current in these cells is mediated by inwardly rectifying Ca(2+)-permeable AMPA receptors. Although GluR5-containing kainate receptors contribute to synaptic currents at high stimulus frequency, they are not required for LTP induction. Glutamatergic synapses on O-LM cells thus behave in a homogeneous manner and exhibit LTP dependent on Ca(2+)-permeable AMPA receptors.

  16. Neonatal Immune Tolerance Induction to Allow Long-Term Studies With an Immunogenic Therapeutic Monoclonal Antibody in Mice.

    PubMed

    Piccand, Matthieu; Bessa, Juliana; Schick, Eginhard; Senn, Claudia; Bourquin, Carole; Richter, Wolfgang F

    2016-03-01

    The purpose of this study is to test the feasibility of neonatal immune tolerance induction in mice to enable long-term pharmacokinetic studies with immunogenic therapeutic monoclonal antibodies (mAb). Neonatal immune tolerance was induced by transfer of a mAb to neonatal mice via colostrum from nursing mother mice treated with two subcutaneous doses of a tolerogen starting within the first 24 h after delivery. Adalimumab and efalizumab were administered as tolerogens at various dose levels. Tolerance induction was evaluated in the offspring after reaching adulthood at 8 weeks of age. After a single intravenous injection of the same mAb as used for tolerance induction, the pharmacokinetics of the mAb and formation of anti-drug antibodies (ADA) in plasma were assessed using ELISA. Tolerance induction to adalimumab was achieved in a maternal dose-dependent manner. Adalimumab immune-tolerant offspring showed a slower adalimumab clearance (4.24 ± 0.32 mL/day/kg) as compared to the control group (12.09 ± 3.81 mL/day/kg). In the control group, accelerated clearance started 7 days after adalimumab dosing, whereas immune-tolerant offspring showed a log-linear terminal concentration-time course. In the offspring, the absence of predose ADA levels was indicative of successful tolerance induction. The second test compound efalizumab was not immunogenic in mice under our experimental conditions. Overall, the present study demonstrated the suitability of neonatal immune tolerance induction for a 4-week single dose study in adult mice with a human therapeutic mAb that is otherwise immunogenic in laboratory animals.

  17. Cooperativity between hippocampal-prefrontal short-term plasticity through associative long-term potentiation.

    PubMed

    Kawashima, Hitoshi; Izaki, Yoshinori; Grace, Anthony A; Takita, Masatoshi

    2006-09-13

    The hippocampal-medial prefrontal cortex (mPFC) pathway provides highly convergent input to the mPFC in rats and shows two types of short-term plasticity in terms of paired-pulse facilitation (PPF) of the field potential under urethane anesthesia. We now report that stimulating either the dorsal or ventral subregions of the posterior hippocampus elicited PPF (by about 335 and 120%, respectively) of field potentials recorded in the mPFC at 100 ms interpulse interval. This PPF-like interaction occurred when projections were stimulated in the ventral-dorsal order (by about 200% of the single-pulsed response), but not vice versa. When weak long-term potentiation (LTP) of the dorsal projection was evoked simultaneously with strong LTP of the ventral projection, an associative effect was revealed (about +55%), although the magnitudes of LTP in each projection were not correlated. Even when the impermutable PPF-like facilitation was further enhanced (by about +120%), the enhancement was not correlated with either form of LTP, but exhibited the interaction of changes in the dorsal PPF, rather than in the heterotopic priming effect through the ventral projection. Moreover, this change was correlated with the associated LTP ratio of dorsal to ventral projection LTP (i.e., LTP associativity). Larger increases in LTP associativity correlated with greater impermutable PPF-like facilitation; in addition, there was hardly attenuation of the response to the dorsal projection by subsequent electrolytic lesions of the ventral subregion. These results indicate that the mPFC functionally integrates discrete sources of hippocampal information via cooperativity between short- and long-term plasticity.

  18. Deficiency of lipid phosphatase SHIP enables long-term reconstitution of hematopoietic inductive bone marrow microenvironment.

    PubMed

    Liang, Olin D; Lu, Jiayun; Nombela-Arrieta, César; Zhong, Jia; Zhao, Li; Pivarnik, Gregory; Mondal, Subhanjan; Chai, Li; Silberstein, Leslie E; Luo, Hongbo R

    2013-05-28

    A dysfunctional bone marrow (BM) microenvironment is thought to contribute to the development of hematologic diseases. However, functional replacement of pathologic BM microenvironment through BM transplantation has not been possible. Furthermore, the study of hematopoietic inductive BM microenvironment is hampered by the lack of a functional nonhematopoietic reconstitution system. Here, we show that a deficiency of SH2-containing inositol-5'-phosphatase-1 (SHIP) in a nonhematopoietic host microenvironment enables its functional reconstitution by wild-type donor cells. This microenvironment reconstitution normalizes hematopoiesis in peripheral blood and BM and alleviates pathology of spleen and lung in the SHIP-deficient recipients. SHIP-deficient BM contains a significantly smaller population of multipotent stromal cells with distinct properties, which may contribute to the reconstitution by wild-type cells. We further demonstrate that it is the nonhematopoietic donor cells that are responsible for the reconstitution. Thus, we have established a nonhematopoietic BM microenvironment reconstitution system to functionally study specific cell types in hematopoietic niches.

  19. Electrophysiological evidence of biphasic action of carnosine on long-term potentiation in urethane-anesthetized rats.

    PubMed

    Suer, Cem; Dolu, Nazan; Artis, A Seda; Sahin, Leyla; Aydogan, Sami

    2011-02-01

    Carnosine is a dipeptide synthesized by the carnosine synthetase from β-alanine and l-histidine. The well-known effects of carnosine may be related with mechanisms producing long-term potentiation which is one of the electrophysiological signs of memory. In the present study we aimed to investigate the effect of four different doses of carnosine on long-term potentiation in urethane-anesthetized rat. A bipolar stimulating electrode was placed in the medial perforant path and a double-barrel glass micropipette was placed in the dentate gyrus as the recording electrode. Artificial cerebrospinal fluid (in the control group) or carnosine (0.1, 1, 10, and 100μg/μL) was infused into the dentate gyrus. Our results showed that the I/O curve of the excitatory postsynaptic potential slope or population spike amplitude was not significantly shifted by carnosine. We found that population spike amplitude increased to 244% and 287% at the dose of 100μg/μL in the post-tetanic and induction phases, respectively, but decreased to 163% and 186% at the dose of 0.1μg/μL and to 145% and 162% at the dose of 1μg/μL when compared with 203% and 232% of the control values. However, there were no significant differences for the slope of excitatory postsynaptic potential. Carnosine had no effect on the EPSP slope or PS amplitude recorded from the dentate gyrus in response to test stimuli when high-frequency stimulation was not delivered. In the present study, we speculated that the effects of carnosine in lower or higher doses could be explained by its effect on different processes, such as soluble guanylyl cyclase inhibition or the conversion of carnosine into histamine.

  20. Potential of "lure and kill" in long-term pest management and eradication of invasive species.

    PubMed

    El-Sayed, A M; Suckling, D M; Byers, J A; Jang, E B; Wearing, C H

    2009-06-01

    "Lure and kill" technology has been used for several decades in pest management and eradication of invasive species. In lure and kill, the insect pest attracted by a semiochemical lure is not "entrapped" at the source of the attractant as in mass trapping, but instead the insect is subjected to a killing agent, which eliminates affected individuals from the population after a short period. In past decades, a growing scientific literature has been published on this concept. This article provides the first review on the potential of lure and kill in long-term pest management and eradication of invasive species. We present a summary of lure and kill, either when used as a stand-alone control method or in combination with other methods. We discuss its efficacy in comparison with other control methods. Several case studies in which lure and kill has been used with the aims of long-term pest management (e.g., pink bollworm, Egyptian cotton leafworm, codling moth, apple maggot, biting flies, and bark beetles) or the eradication of invasive species (e.g., tephritid fruit flies and boll weevils) are provided. Subsequently, we identify essential knowledge required for successful lure and kill programs that include lure competitiveness with natural odor source; lure density; lure formulation and release rate; pest population density and risk of immigration; and biology and ecology of the target species. The risks associated with lure and kill, especially when used in the eradication programs, are highlighted. We comment on the cost-effectiveness of this technology and its strengths and weaknesses, and list key reasons for success and failure. We conclude that lure and kill can be highly effective in controlling small, low-density, isolated populations, and thus it has the potential to add value to long-term pest management. In the eradication of invasive species, lure and kill offers a major advantage in effectiveness by its being inverse density dependent and it provides

  1. Expression mechanisms underlying long-term potentiation: a postsynaptic view, 10 years on.

    PubMed

    Granger, Adam J; Nicoll, Roger A

    2014-01-05

    This review focuses on the research that has occurred over the past decade which has solidified a postsynaptic expression mechanism for long-term potentiation (LTP). However, experiments that have suggested a presynaptic component are also summarized. It is argued that the pairing of glutamate uncaging onto single spines with postsynaptic depolarization provides the final and most elegant demonstration of a postsynaptic expression mechanism for NMDA receptor-dependent LTP. The fact that the magnitude of this LTP is similar to that evoked by pairing synaptic stimulation and depolarization leaves little room for a substantial presynaptic component. Finally, recent data also require a revision in our thinking about the way AMPA receptors (AMPARs) are recruited to the postsynaptic density during LTP. This recruitment is independent of subunit type, but does require an adequate reserve pool of extrasynaptic receptors.

  2. Taurine rescues hippocampal long-term potentiation from ammonia-induced impairment.

    PubMed

    Chepkova, Aisa N; Sergeeva, Olga A; Haas, Helmut L

    2006-09-01

    Hyperammonemia, a major pathophysiological factor in hepatic encephalopathy, impairs long-term potentiation (LTP) of synaptic transmission, a cellular model of learning and memory, in the hippocampus. We have now studied the protective action of taurine on this paradigm by analyzing LTP characteristics in mouse hippocampal slices treated with ammonium chloride (1 mM) in the presence of taurine (1 mM), an ubiquitous osmolyte, antioxidant, and neuromodulator, as well as other substances with such properties. Ammonia-treated slices displayed a significant impairment of LTP maintenance. Taurine and the mitochondrial enhancer l-carnitine, but not the antioxidants (ascorbate, carnosine, and the novel compound GVS-111) or the osmolyte betaine prevented this impairment. The protective effect of taurine was preserved under the blockade of inhibitory GABA(A) and glycine receptors. It is suggested that taurine may rescue the mechanisms of hippocampal synaptic plasticity by improving mitochondrial function under hyperammonemic conditions.

  3. Synaptic Disinhibition During Maintenance of Long-Term Potentiation in the CA1 Hippocampal Subfield

    NASA Astrophysics Data System (ADS)

    Stelzer, Armin; Simon, Gabor; Kovacs, Gabor; Rai, Rabindra

    1994-04-01

    Long-term potentiation (LTP) in the CA1 region of the hippocampus is widely believed to occur through a strengthening of efficacy of excitatory synapses between afferent fibers and pyramidal cells. An alternative mechanism of LTP, reduction of efficacy of synaptic inhibition, was examined in the present report. The present study demonstrates that the maintenance of LTP in the CA1 hippocampal subfield of guinea pigs is accompanied by impairment of type A γ-aminobutyric acid (GABA) receptor function, particularly at apical dendritic sites of CA1 pyramidal cells. Enhanced excitability of GABAergic interneurons during LTP represents a strengthening of inhibitory efficacy. The net effect of opposite modifications of synaptic inhibition during LTP of CA1 pyramidal cells is an overall impairment of the strength of GABAergic inhibition, and disinhibition could contribute importantly to CA1 pyramidal cell LTP.

  4. Identification of compounds that potentiate CREB signaling as possible enhancers of long-term memory

    PubMed Central

    Xia, Menghang; Huang, Ruili; Guo, Vicky; Southall, Noel; Cho, Ming-Hsuang; Inglese, James; Austin, Christopher P.; Nirenberg, Marshall

    2009-01-01

    Many studies have implicated the cAMP Response Element Binding (CREB) protein signaling pathway in long-term memory. To identify small molecule enhancers of CREB activation of gene expression, we screened ≈73,000 compounds, each at 7–15 concentrations in a quantitative high-throughput screening (qHTS) format, for activity in cells by assaying CREB mediated β-lactamase reporter gene expression. We identified 1,800 compounds that potentiated CREB mediated gene expression, with potencies as low as 16 nM, comprising 96 structural series. Mechanisms of action were systematically determined, and compounds that affect phosphodiesterase 4, protein kinase A, and cAMP production were identified, as well as compounds that affect CREB signaling via apparently unidentified mechanisms. qHTS folowed by interrogation of pathway targets is an efficient paradigm for lead generation for chemical genomics and drug development. PMID:19196967

  5. Potential Cascading Failures of Long-term Shoreline Stabilization in a Coupled Morphoeconomic Coastline Evolution Model

    NASA Astrophysics Data System (ADS)

    Ells, K. D.; McNamara, D.; Murray, A.

    2013-12-01

    Systems with many interconnected parts can be susceptible to a cascade of failures, where the failure of one or more constituents can trigger the failure of others. This phenomenon has received significant attention in various applications of complex networks, but for many environmental systems the component parts and extent of their connectivity are not readily evident. Recent modeling work has shown that the evolution of many large-scale coastline shapes can be understood by the directional distribution of waves reaching the coast from offshore (i.e. wave climate), and that coastal communities responding to erosion with long-term shoreline stabilization (e.g. beach nourishment or seawalls) may perturb patterns of shoreline change far from their own locality. Economic strategies for shoreline stabilization - historically a spatially decentralized practice - are subject to constraints ranging from the scarcity of nourishment sand to coastal property values and locally observed erosion rates. Initial investigations into the coupling between large-scale coastline morphology and coastal economies along a cuspate cape coastline (similar to the Carolina capes, USA) have shown that long-term beach nourishment can become unsustainable due to the depletion of a finite sand reservoir, and that the spatial dynamics of abandonment depend on the distribution of both erosion rates and property values. Here we extend this analysis to consider: 1) how the abandonment of beach nourishment in one location may induce increased nourishment rates and potential abandonment in other locations alongshore, and 2) the consequences of hard-structured alternatives to beach nourishment (e.g. seawalls). The potential for cascading effects may be most significant along coastlines with subtle curvature and wave climates dominated by low-angle waves, broadly similar to much of the New Jersey and Delmarva coasts, USA, a region with a complex history of shoreline stabilization.

  6. Primary Blast Exposure Increases Hippocampal Vulnerability to Subsequent Exposure: Reducing Long-Term Potentiation.

    PubMed

    Effgen, Gwen B; Ong, Tiffany; Nammalwar, Shruthi; Ortuño, Andrea I; Meaney, David F; 'Dale' Bass, Cameron R; Morrison, Barclay

    2016-10-15

    Up to 80% of injuries sustained by U.S. soldiers in Operation Enduring Freedom and Operation Iraqi Freedom were the result of blast exposure from improvised explosive devices. Some soldiers experience multiple blasts while on duty, and it has been suggested that symptoms of repetitive blast are similar to those that follow multiple non-blast concussions, such as sport-related concussion. Despite the interest in the effects of repetitive blast exposure, it remains unknown whether an initial blast renders the brain more vulnerable to subsequent exposure, resulting in a synergistic injury response. To investigate the effect of multiple primary blasts on the brain, organotypic hippocampal slice cultures were exposed to single or repetitive (two or three total) primary blasts of varying intensities. Long-term potentiation was significantly reduced following two Level 2 (92.7 kPa, 1.4 msec, 38.5 kPa·msec) blasts delivered 24 h apart without altering basal evoked response. This deficit persisted when the interval between injuries was increased to 72 h but not when the interval was extended to 144 h. The repeated blast exposure with a 24 h interval increased microglia staining and activation significantly but did not significantly increase cell death or damage axons, dendrites, or principal cell layers. Lack of overt structural damage and change in basal stimulated neuron response suggest that injury from repetitive primary blast exposure may specifically affect long-term potentiation. Our studies suggest repetitive primary blasts can exacerbate injury dependent on the injury severity and interval between exposures.

  7. Post-ischaemic long-term synaptic potentiation in the striatum: a putative mechanism for cell type-specific vulnerability.

    PubMed

    Calabresi, Paolo; Saulle, Emilia; Centonze, Diego; Pisani, Antonio; Marfia, Girolama A; Bernardi, Giorgio

    2002-04-01

    In the present in vitro study of rat brain, we report that transient oxygen and glucose deprivation (in vitro ischaemia) induced a post-ischaemic long-term synaptic potentiation (i-LTP) at corticostriatal synapses. We compared the physiological and pharmacological characteristics of this pathological form of synaptic plasticity with those of LTP induced by tetanic stimulation of corticostriatal fibres (t-LTP), which is thought to represent a cellular substrate of learning and memory. Activation of N-methyl-D-aspartate (NMDA) receptors was required for the induction of both forms of synaptic plasticity. The intraneuronal injection of the calcium chelator BAPTA [bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetate] and inhibitors of the mitogen-activated protein kinase pathway blocked both forms of synaptic plasticity. However, while t-LTP showed input specificity, i-LTP occurred also at synaptic pathways inactive during the ischaemic period. In addition, scopolamine, a muscarinic receptor antagonist, prevented the induction of t-LTP but not of i-LTP, indicating that endogenous acetylcholine is required for physiological but not for pathological synaptic potentiation. Finally, we found that striatal cholinergic interneurones, which are resistant to in vivo ischaemia, do not express i-LTP while they express t-LTP. We suggest that i-LTP represents a pathological form of synaptic plasticity that may account for the cell type-specific vulnerability observed in striatal spiny neurones following ischaemia and energy deprivation.

  8. Theta pulse stimulation: a natural stimulus pattern can trigger long-term depression but fails to reverse long-term potentiation in morphine withdrawn hippocampus area CA1.

    PubMed

    Hosseinmardi, Narges; Fathollahi, Yaghoub; Naghdi, Nasser; Javan, Mohammad

    2009-11-03

    The effects of chronic morphine exposure on synaptic plasticity in the CA1 region of the hippocampal slice preparation using extracellular recordings of the population spike (PS) evoked in response to Schaffer collateral stimulation were studied. High frequency stimulation (HFS; 1X100 Hz) and theta pulse stimulation (TPS; 5 Hz trains for 3 min) were used as patterned activities. The results showed that in rats chronically treated with morphine (dependent group), TPS induced long-term depression (LTD) of PS in CA1 in the absence of in vitro morphine. This TPS-induced PS LTD was blocked in the presence of either AP5 (NMDAR antagonist) or CPX (A1 adenosine receptor antagonist) alone, but was not blocked when AP5 and CPX were co-applied. This TPS-induced PS LTD was also blocked in the presence of either 8-PT (a selective A1 adenosine receptor antagonist) or MRS1220 (a specific A3 receptor antagonist). Additionally, when TPS was applied prior to HFS, PS long-term potentiation (LTP) was blocked. However, when TPS was applied after HFS, there was no reversal of PS LTP in slices from dependent rats in contrast to controls which displayed reversal of LTP. Both the PS LTD and the absence of PS LTP reversal were blocked by in vitro application of morphine. It is concluded that morphine withdrawal was associated with greater depression of CA1 PS elicited by natural stimulus induced activity pattern. This effect was associated with changes in NMDA and adenosine receptors due to chronic morphine administration. Such an in vitro preparation could provide a novel paradigm to investigate withdrawal effects on synaptic plasticity.

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

    NASA Astrophysics Data System (ADS)

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

    2016-04-01

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

  10. Activation of Muscarinic M1 Acetylcholine Receptors Induces Long-Term Potentiation in the Hippocampus

    PubMed Central

    Dennis, Siobhan H.; Pasqui, Francesca; Colvin, Ellen M.; Sanger, Helen; Mogg, Adrian J.; Felder, Christian C.; Broad, Lisa M.; Fitzjohn, Steve M.; Isaac, John T.R.; Mellor, Jack R.

    2016-01-01

    Muscarinic M1 acetylcholine receptors (M1Rs) are highly expressed in the hippocampus, and their inhibition or ablation disrupts the encoding of spatial memory. It has been hypothesized that the principal mechanism by which M1Rs influence spatial memory is by the regulation of hippocampal synaptic plasticity. Here, we use a combination of recently developed, well characterized, selective M1R agonists and M1R knock-out mice to define the roles of M1Rs in the regulation of hippocampal neuronal and synaptic function. We confirm that M1R activation increases input resistance and depolarizes hippocampal CA1 pyramidal neurons and show that this profoundly increases excitatory postsynaptic potential-spike coupling. Consistent with a critical role for M1Rs in synaptic plasticity, we now show that M1R activation produces a robust potentiation of glutamatergic synaptic transmission onto CA1 pyramidal neurons that has all the hallmarks of long-term potentiation (LTP): The potentiation requires NMDA receptor activity and bi-directionally occludes with synaptically induced LTP. Thus, we describe synergistic mechanisms by which acetylcholine acting through M1Rs excites CA1 pyramidal neurons and induces LTP, to profoundly increase activation of CA1 pyramidal neurons. These features are predicted to make a major contribution to the pro-cognitive effects of cholinergic transmission in rodents and humans. PMID:26472558

  11. Activation of Muscarinic M1 Acetylcholine Receptors Induces Long-Term Potentiation in the Hippocampus.

    PubMed

    Dennis, Siobhan H; Pasqui, Francesca; Colvin, Ellen M; Sanger, Helen; Mogg, Adrian J; Felder, Christian C; Broad, Lisa M; Fitzjohn, Steve M; Isaac, John T R; Mellor, Jack R

    2016-01-01

    Muscarinic M1 acetylcholine receptors (M1Rs) are highly expressed in the hippocampus, and their inhibition or ablation disrupts the encoding of spatial memory. It has been hypothesized that the principal mechanism by which M1Rs influence spatial memory is by the regulation of hippocampal synaptic plasticity. Here, we use a combination of recently developed, well characterized, selective M1R agonists and M1R knock-out mice to define the roles of M1Rs in the regulation of hippocampal neuronal and synaptic function. We confirm that M1R activation increases input resistance and depolarizes hippocampal CA1 pyramidal neurons and show that this profoundly increases excitatory postsynaptic potential-spike coupling. Consistent with a critical role for M1Rs in synaptic plasticity, we now show that M1R activation produces a robust potentiation of glutamatergic synaptic transmission onto CA1 pyramidal neurons that has all the hallmarks of long-term potentiation (LTP): The potentiation requires NMDA receptor activity and bi-directionally occludes with synaptically induced LTP. Thus, we describe synergistic mechanisms by which acetylcholine acting through M1Rs excites CA1 pyramidal neurons and induces LTP, to profoundly increase activation of CA1 pyramidal neurons. These features are predicted to make a major contribution to the pro-cognitive effects of cholinergic transmission in rodents and humans.

  12. Prolonged ampakine exposure prunes dendritic spines and increases presynaptic release probability for enhanced long-term potentiation in the hippocampus.

    PubMed

    Chang, Philip K-Y; Prenosil, George A; Verbich, David; Gill, Raminder; McKinney, R Anne

    2014-09-01

    CX 546, an allosteric positive modulator of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type ionotropic glutamate receptors (AMPARs), belongs to a drug class called ampakines. These compounds have been shown to enhance long-term potentiation (LTP), a cellular model of learning and memory, and improve animal learning task performance, and have augmented cognition in neurodegenerative patients. However, the chronic effect of CX546 on synaptic structures has not been examined. The structure and integrity of dendritic spines are thought to play a role in learning and memory, and their abnormalities have been implicated in cognitive disorders. In addition, their structural plasticity has been shown to be important for cognitive function, such that dendritic spine remodeling has been proposed as the morphological correlate for LTP. Here, we tested the effect of CX546 on dendritic spine remodeling following long-term treatment. We found that, with prolonged CX546 treatment, organotypic hippocampal slice cultures showed a significant reduction in CA3-CA1 excitatory synapse and spine density. Electrophysiological approaches revealed that the CA3-CA1 circuitry compensates for this synapse loss by increasing synaptic efficacy through enhancement of presynaptic release probability. CX546-treated slices showed prolonged and enhanced potentiation upon LTP induction. Furthermore, structural plasticity, namely spine head enlargement, was also more pronounced after CX546 treatment. Our results suggest a concordance of functional and structural changes that is enhanced with prolonged CX546 exposure. Thus, the improved cognitive ability of patients receiving ampakine treatment may result from the priming of synapses through increases in the structural plasticity and functional reliability of hippocampal synapses.

  13. Induction of long-term immunity against respiratory syncytial virus glycoprotein by an osmotic polymeric nanocarrier.

    PubMed

    Firdous, Jannatul; Islam, Mohammad Ariful; Park, Sung-Moo; Cheon, In-Su; Shim, Byoung-Shik; Yoon, Hyo-Shin; Song, Manki; Chang, Jun; Choi, Yun-Jaie; Park, Yeong-Min; Boraschi, Diana; Han, Seung-Hyun; Cho, Chong-Su; Yun, Cheol-Heui

    2014-11-01

    Respiratory syncytial virus (RSV) is one of the most common causes of viral deaths in infants worldwide, yet no effective vaccines are available. Here, we report an osmotically active polysaccharide-based polysorbitol transporter (PST) prepared from sorbitol diacrylate and low-molecular-weight polyethylenimine (PEI) showing a potent, yet safe, adjuvant activity and acting as an effective delivery tool for RSV glycoprotein (RGp) antigen. PST showed no toxicity in vitro or in vivo, unlike PEI and the well-known experimental mucosal adjuvant cholera toxin (CT). PST formed nano-sized complexes with RGp by simple mixing, without affecting antigenic stability. The complexes exhibited negative surface charges that made them highly efficient in the selective activation of phagocytic cells and enhancement of phagocytic uptake. This resulted in an improved cytokine production and in the significant augmentation of RGp-specific antibody production, which persisted for over 200 days. Interestingly, PST/RGp enhanced phagocytic uptake owing to the osmotic property of PST and its negative zeta potential, suggesting that PST could selectively stimulate phagocytic cells, thereby facilitating a long-lived antigen-specific immune response, which was presumably further enhanced by the polysaccharide properties of PST.

  14. Long-term stability, biocompatibility and oral delivery potential of risperidone-loaded solid lipid nanoparticles.

    PubMed

    Silva, A C; Kumar, A; Wild, W; Ferreira, D; Santos, D; Forbes, B

    2012-10-15

    A solid lipid nanoparticles (SLN) formulation to improve the oral delivery of risperidone (RISP), a poorly water-soluble drug, was designed and tested. Initially, lipid-RISP solubility was screened to select the best lipid for SLN preparation. Compritol(®)-based formulations were chosen and their long-term stability was assessed over two years of storage (at 25 °C and 4 °C) by means of particle size, polydispersity index (PI), zeta potential (ZP) and encapsulation efficiency (EE) measurements. SLN shape was observed by transmission electron microscopy (TEM) at the beginning and end of the study. The oxidative potential (OP) of the SLN was measured and their biocompatibility with Caco-2 cells was evaluated using the (4,5-dimethylthiazol-2-yl)2,5-dyphenyl-tetrazolium bromide (MTT) assay. In vitro drug release and transport studies were performed to predict the in vivo release profile and to evaluate the drug delivery potential of the SLN formulations, respectively. The RISP-loaded SLN systems were stable and had high EE and similar shape to the placebo formulations before and after storage. Classical Fickian diffusion was identified as the release mechanism for RISP from the SLN formulation. Biocompatibility and dose-dependent RISP transport across Caco-2 cells were observed for the prepared SLN formulations. The viability of SLN as formulations for oral delivery of poorly water-soluble drugs such as RISP was illustrated.

  15. Long-term climate change mitigation potential with organic matter management on grasslands.

    PubMed

    Ryals, Rebecca; Hartman, Melannie D; Parton, William J; DeLonge, Marcia S; Silver, Whendee L

    2015-03-01

    Compost amendments to grasslands have been proposed as a strategy to mitigate climate change through carbon (C) sequestration, yet little research exists exploring the net mitigation potential or the long-term impacts of this strategy. We used field data and the DAYCENT biogeochemical model to investigate the climate change mitigation potential of compost amendments to grasslands in California, USA. The model was used to test ecosystem C and greenhouse gas responses to a range of compost qualities (carbon to nitrogen [C:N] ratios of 11.1, 20, or 30) and application rates (single addition of 14 Mg C/ha or 10 annual additions of 1.4 Mg C · ha(-1) · yr(-1)). The model was parameterized using site-specific weather, vegetation, and edaphic characteristics and was validated by comparing simulated soil C, nitrous oxide (N2O), methane (CH4), and carbon dioxide (CO2) fluxes, and net primary production (NPP) with three years of field data. All compost amendment scenarios led to net greenhouse gas sinks that persisted for several decades. Rates of climate change mitigation potential ranged from 130 ± 3 g to 158 ± 8 g CO2-eq · m(-2) ·yr(-1) (where "eq" stands for "equivalents") when assessed over a 10-year time period and 63 ± 2 g to 84 ± 10 g CO2- eq · m(-2) · yr(-1) over a 30-year time period. Both C storage and greenhouse gas emissions increased rapidly following amendments. Compost amendments with lower C:N led to higher C sequestration rates over time. However, these soils also experienced greater N20 fluxes. Multiple smaller compost additions resulted in similar cumulative C sequestration rates, albeit with a time lag, and lower cumulative N2O emissions. These results identify a trade-off between maximizing C sequestration and minimizing N2O emissions following amendments, and suggest that compost additions to grassland soils can have a long-term impact on C and greenhouse gas dynamics that contributes to climate change mitigation.

  16. Long-term potentiation of glycinergic synapses triggered by interleukin 1β

    PubMed Central

    Chirila, Anda M.; Brown, Travis E.; Bishop, Rachel A.; Bellono, Nicholas W.; Pucci, Francesco G.; Kauer, Julie A.

    2014-01-01

    Long-term potentiation (LTP) is a persistent increase in synaptic strength required for many behavioral adaptations, including learning and memory, visual and somatosensory system functional development, and drug addiction. Recent work has suggested a role for LTP-like phenomena in the processing of nociceptive information in the dorsal horn and in the generation of central sensitization during chronic pain states. Whereas LTP of glutamatergic and GABAergic synapses has been characterized throughout the central nervous system, to our knowledge there have been no reports of LTP at mammalian glycinergic synapses. Glycine receptors (GlyRs) are structurally related to GABAA receptors and have a similar inhibitory role. Here we report that in the superficial dorsal horn of the spinal cord, glycinergic synapses on inhibitory GABAergic neurons exhibit LTP, occurring rapidly after exposure to the inflammatory cytokine interleukin-1 beta. This form of LTP (GlyR LTP) results from an increase in the number and/or change in biophysical properties of postsynaptic glycine receptors. Notably, formalin-induced peripheral inflammation in vivo potentiates glycinergic synapses on dorsal horn neurons, suggesting that GlyR LTP is triggered during inflammatory peripheral injury. Our results define a previously unidentified mechanism that could disinhibit neurons transmitting nociceptive information and may represent a useful therapeutic target for the treatment of pain. PMID:24830427

  17. Long-term stability of nanostructured thin film electrodes at operating potentials

    DOE PAGES

    Ahluwalia, Rajesh K.; Peng, J. -K.; Wang, X.; ...

    2017-02-09

    Long-term stability of nanostructured thin film (NSTF) catalysts at operating potentials has been investigated. Compared to high surface area Pt/C catalysts, NSTF electrodes show 20–50x smaller F– emission rates (FER) because of their high specific activity for oxygen reduction reaction (ORR), but are susceptible to poisoning by the products of membrane degradation because of their low electrochemically active surface area (ECSA). The observed voltage degradation rates at potentials corresponding to 1–1.5 A/cm2 current density are much higher than the allowable 13–14 μV/h. Although F– is not itself responsible for performance decay, cumulative fluoride release (CFR) is a good marker formore » catalyst surface contamination. The observed performance decay is not only due to loss of active Pt sites but also adsorbed impurities impeding ORR kinetics. There is a strong correlation between measured CFR and observed decrease in specific ORR activity and limiting current density and increase in mass transfer overpotentials. Furthermore, the correlations indicate that the target of <10% lifetime performance degradation can be achieved by restricting CFR in NSTF electrodes to 0.7 μg/cm2, as may be possible with more stable membranes, higher surface area NSTF catalysts, and cell operation at lower temperatures and higher relative humidities.« less

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

    PubMed

    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.

  19. Both NR2A and NR2B Subunits of the NMDA Receptor Are Critical for Long-Term Potentiation and Long-Term Depression in the Lateral Amygdala of Horizontal Slices of Adult Mice

    ERIC Educational Resources Information Center

    Muller, Tobias; Albrecht, Doris; Gebhardt, Christine

    2009-01-01

    The lateral nucleus of the amygdala (LA) is implicated in emotional and social behaviors. We recently showed that in horizontal brain slices, activation of NMDA receptors (NMDARs) is a requirement for persistent synaptic alterations in the LA, such as long-term potentiation (LTP) and long-term depression (LTD). In the LA, NR2A- and NR2B-type NMDRs…

  20. Human color vision deficits induced by accidental laser exposure and potential for long-term recovery

    NASA Astrophysics Data System (ADS)

    Zwick, Harry; Lund, Brian J.; Brown, Jeremiah, Jr.; Stuck, Bruce E.; Loveday, J.

    2003-06-01

    Purpose: To evaluate long term deficits in human color discrimination induced by accidental laser macular damage and assess potential for recovery of color vision deficits. Methods: Nine laser accident cases (Q-switched Neodymium) presenting initially with confined or vitreous macular hemorrhage were evaluated with the Farnsworth-Munsell 100 Hue test within 2 days to 3 months post exposure. Both total as well as partial errors in the blue/yellow (B/Y) and red/green (R/G) regions were assessed. Independent assessment of axis orientation and complexity were obtained via a Fourier series expansion of error scores. Comparisons of both total and partial B/Y and R/G errors were made with age matched normal subjects, idiopathic and juvenile onset macular holes. Confocal Scanning Laser Ophthalmoscopy and Optical Coherence Tomography characterized the presence of retinal traction, intraretinal scar, macular thickness and macular hole formation. Results: Comparison of exposed and non-exposed age matched individuals were significant (P<.001) for both total and partial errors. In four cases where macular injury ranged from mild scar to macular hole, color discrimination errors achieved normal levels in 1 to 12 months post exposure. A mild tritan axis, dominant B/Y ("blue/yellow") errors, and retinal traction were observed in a macular hole case. At 12 months post exposure, traction about the hole disappeared, and total and partial errors were normal. Where damage involved a greater degree of scarring, retinal traction and multiple injury sites, long term recovery of total and partial error recovery was retarded with complex axis makeup. Single exposures in the paramacula produced tritan axes, while multiple exposures within and external to the macula increased total and partial R/G ("red/green") error scores. Total errors increased when paramacular hole enlargement induced macular traction. Such hole formation produced significant increases in total errors, complex axis

  1. The reemergence of long-term potentiation in aged Alzheimer’s disease mouse model

    PubMed Central

    Huh, Seonghoo; Baek, Soo-Ji; Lee, Kyung-Hwa; Whitcomb, Daniel J.; Jo, Jihoon; Choi, Seong-Min; Kim, Dong Hyun; Park, Man-Seok; Lee, Kun Ho; Kim, Byeong C.

    2016-01-01

    Mouse models of Alzheimer’s disease (AD) have been developed to study the pathophysiology of amyloid β protein (Aβ) toxicity, which is thought to cause severe clinical symptoms such as memory impairment in AD patients. However, inconsistencies exist between studies using these animal models, specifically in terms of the effects on synaptic plasticity, a major cellular model of learning and memory. Whereas some studies find impairments in plasticity in these models, others do not. We show that long-term potentiation (LTP), in the CA1 region of hippocampal slices from this mouse, is impared at Tg2576 adult 6–7 months old. However, LTP is inducible again in slices taken from Tg2576 aged 14–19 months old. In the aged Tg2576, we found that the percentage of parvalbumin (PV)-expressing interneurons in hippocampal CA1-3 region is significantly decreased, and LTP inhibition or reversal mediated by NRG1/ErbB signaling, which requires ErbB4 receptors in PV interneurons, is impaired. Inhibition of ErbB receptor kinase in adult Tg2576 restores LTP but impairs depotentiation as shown in aged Tg2576. Our study suggests that hippocampal LTP reemerges in aged Tg2576. However, this reemerged LTP is an insuppressible form due to impaired NRG1/ErbB signaling, possibly through the loss of PV interneurons. PMID:27377368

  2. Inducible molecular switches for the study of long-term potentiation.

    PubMed

    Hédou, Gaël; Mansuy, Isabelle M

    2003-04-29

    This article reviews technical and conceptual advances in unravelling the molecular bases of long-term potentiation (LTP), learning and memory using genetic approaches. We focus on studies aimed at testing a model suggesting that protein kinases and protein phosphatases balance each other to control synaptic strength and plasticity. We describe how gene 'knock-out' technology was initially exploited to disrupt the Ca(2+)/calmodulin-dependent protein kinase IIalpha (CaMKIIalpha) gene and how refined knock-in techniques later allowed an analysis of the role of distinct phosphorylation sites in CaMKII. Further to gene recombination, regulated gene expression using the tetracycline-controlled transactivator and reverse tetracycline-controlled transactivator systems, a powerful new means for modulating the activity of specific molecules, has been applied to CaMKIIalpha and the opposing protein phosphatase calcineurin. Together with electro-physiological and behavioural evaluation of the engineered mutant animals, these genetic methodologies have helped gain insight into the molecular mechanisms of plasticity and memory. Further technical developments are, however, awaited for an even higher level of finesse.

  3. Spike timing-dependent long-term potentiation in ventral tegmental area dopamine cells requires PKC.

    PubMed

    Luu, Percy; Malenka, Robert C

    2008-07-01

    Long-term potentiation (LTP) of excitatory synapses on ventral tegmental area (VTA) dopamine (DA) cells is thought to play an important role in mediating some of the behavioral effects of drugs of abuse yet little is known about its underlying mechanisms. We find that spike timing-dependent LTP (STD LTP) in VTA DA cells is absent in slices prepared from mice previously administered cocaine, suggesting that cocaine-induced LTP and STD LTP share underlying mechanisms. This form of STD LTP is dependent on NMDA receptor (NMDAR) activation and a rise in postsynaptic calcium but surprisingly was not affected by an inhibitor of calcium/calmodulin-dependent protein kinase II (CaMKII). It was blocked by antagonists of conventional isoforms of PKC, whereas activation of protein kinase C (PKC) using a phorbol ester enhanced synaptic strength. These results suggest that NMDAR-mediated activation of PKC, but not CaMKII, is a critical trigger for LTP in VTA DA cells.

  4. Incorporation of inwardly rectifying AMPA receptors at silent synapses during hippocampal long-term potentiation.

    PubMed

    Morita, Daiju; Rah, Jong Cheol; Isaac, John T R

    2014-01-05

    Despite decades of study, the mechanisms by which synapses express the increase in strength during long-term potentiation (LTP) remain an area of intense interest. Here, we have studied how AMPA receptor subunit composition changes during the early phases of hippocampal LTP in CA1 pyramidal neurons. We studied LTP at silent synapses that initially lack AMPA receptors, but contain NMDA receptors. We show that strongly inwardly rectifying AMPA receptors are initially incorporated at silent synapses during LTP and are then subsequently replaced by non-rectifying AMPA receptors. These findings suggest that silent synapses initially incorporate GluA2-lacking, calcium-permeable AMPA receptors during LTP that are then replaced by GluA2-containing calcium-impermeable receptors. We also show that LTP consolidation at CA1 synapses requires a rise in intracellular calcium concentration during the early phase of expression, indicating that calcium influx through the GluA2-lacking AMPA receptors drives their replacement by GluA2-containing receptors during LTP consolidation. Taken together with previous studies in hippocampus and in other brain regions, these findings suggest that a common mechanism for the expression of activity-dependent glutamatergic synaptic plasticity involves the regulation of GluA2-subunit composition and highlights a critical role for silent synapses in this process.

  5. Exposure of mouse to high gravitation forces induces long-term potentiation in the hippocampus.

    PubMed

    Ishii, Masamitsu; Tomizawa, Kazuhito; Matsushita, Masayuki; Matsui, Hideki

    2004-06-01

    The central nervous system is highly plastic and has been shown to undergo both transient and chronic adaptive changes in response to environmental influences. The purpose of this study was to investigate the effect of hypergravic field on long-term potentiation (LTP) in the mouse hippocampus. Exposure of mice to 4G fields for 48 h had no effect on input-output coupling during extracellular stimulation of Schaffer collaterals and paired pulse facilitation, suggesting that the hypergravic exposure had no detrimental effect on basal neurotransmission in the hippocampus. However, the exposure to 4G fields for 48 h significantly induced LTP compared with the control mouse hippocampus. In contrast, no significant changes of late-phase LTP (L-LTP) were found in the hippocampi of mice exposed to the hypergravic field. Exposure of mice to 4G fields for 48 h enhanced AMPA receptor phosphorylation but not cyclic AMP-responsive element binding protein (CREB) phosphorylation. These results suggest that exposure to hyperdynamic fields influences the synaptic plasticity in the hippocampus.

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

    PubMed

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

    2011-06-26

    Memory is believed to occur in the human brain as a result of two types of synaptic plasticity: short-term plasticity (STP) and long-term potentiation (LTP; refs 1-4). In neuromorphic engineering, emulation of known neural behaviour has proven to be difficult to implement in software because of the highly complex interconnected nature of thought processes. Here we report the discovery of a Ag(2)S inorganic synapse, which emulates the synaptic functions of both STP and LTP characteristics through the use of input pulse repetition time. The structure known as an atomic switch, operating at critical voltages, stores information as STP with a spontaneous decay of conductance level in response to intermittent input stimuli, whereas frequent stimulation results in a transition to LTP. The Ag(2)S inorganic synapse has interesting characteristics with analogies to an individual biological synapse, and achieves dynamic memorization in a single device without the need of external preprogramming. A psychological model related to the process of memorizing and forgetting is also demonstrated using the inorganic synapses. Our Ag(2)S element indicates a breakthrough in mimicking synaptic behaviour essential for the further creation of artificial neural systems that emulate characteristics of human memory.

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

    NASA Astrophysics Data System (ADS)

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

    2011-08-01

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

  8. Isolated Primary Blast Inhibits Long-Term Potentiation in Organotypic Hippocampal Slice Cultures.

    PubMed

    Vogel, Edward W; Effgen, Gwen B; Patel, Tapan P; Meaney, David F; Bass, Cameron R Dale; Morrison, Barclay

    2016-04-01

    Over the last 13 years, traumatic brain injury (TBI) has affected over 230,000 U.S. service members through the conflicts in Iraq and Afghanistan, mostly as a result of exposure to blast events. Blast-induced TBI (bTBI) is multi-phasic, with the penetrating and inertia-driven phases having been extensively studied. The effects of primary blast injury, caused by the shockwave interacting with the brain, remain unclear. Earlier in vivo studies in mice and rats have reported mixed results for primary blast effects on behavior and memory. Using a previously developed shock tube and in vitro sample receiver, we investigated the effect of isolated primary blast on the electrophysiological function of rat organotypic hippocampal slice cultures (OHSC). We found that pure primary blast exposure inhibited long-term potentiation (LTP), the electrophysiological correlate of memory, with a threshold between 9 and 39 kPa·ms impulse. This deficit occurred well below a previously identified threshold for cell death (184 kPa·ms), supporting our previously published finding that primary blast can cause changes in brain function in the absence of cell death. Other functional measures such as spontaneous activity, network synchronization, stimulus-response curves, and paired-pulse ratios (PPRs) were less affected by primary blast exposure, as compared with LTP. This is the first study to identify a tissue-level tolerance threshold for electrophysiological changes in neuronal function to isolated primary blast.

  9. Primary Blast Injury Depressed Hippocampal Long-Term Potentiation through Disruption of Synaptic Proteins.

    PubMed

    Vogel, Edward W; Rwema, Steve H; Meaney, David F; Bass, Cameron R Dale; Morrison, Barclay

    2017-03-01

    Blast-induced traumatic brain injury (bTBI) is a major threat to United States service members in military conflicts worldwide. The effects of primary blast, caused by the supersonic shockwave interacting with the skull and brain, remain unclear. Our group has previously reported that in vitro primary blast exposure can reduce long-term potentiation (LTP), the electrophysiological correlate of learning and memory, in rat organotypic hippocampal slice cultures (OHSCs) without significant changes to cell viability or basal, evoked neuronal function. We investigated the time course of primary blast-induced deficits in LTP and the molecular mechanisms that could underlie these deficits. We found that pure primary blast exposure induced LTP deficits in a delayed manner, requiring longer than 1 hour to develop, and that these deficits spontaneously recovered by 10 days following exposure depending on blast intensity. Additionally, we observed that primary blast exposure reduced total α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor 1 (GluR1) subunit expression and phosphorylation of the GluR1 subunit at the serine-831 site. Blast also reduced the expression of postsynaptic density protein-95 (PSD-95) and phosphorylation of stargazin protein at the serine-239/240 site. Finally, we found that modulation of the cyclic adenosine monophosphate (cAMP) pathway ameliorated electrophysiological and protein-expression changes caused by blast. These findings could inform the development of novel therapies to treat blast-induced loss of neuronal function.

  10. Characterization of a Fetal Liver Cell Population Endowed with Long-Term Multiorgan Endothelial Reconstitution Potential.

    PubMed

    Cañete, Ana; Comaills, Valentine; Prados, Isabel; Castro, Ana María; Hammad, Seddik; Ybot-Gonzalez, Patricia; Bockamp, Ernesto; Hengstler, Jan G; Gottgens, Bertie; Sánchez, María José

    2017-02-01

    Stable reconstitution of vascular endothelial beds upon transplantation of progenitor cells represents an important challenge due to the paucity and generally limited integration/expansion potential of most identified vascular related cell subsets. We previously showed that mouse fetal liver (FL) hemato/vascular cells from day 12 of gestation (E12), expressing the Stem Cell Leukaemia (SCL) gene enhancer transgene (SCL-PLAP(+) cells), had robust endothelial engraftment potential when transferred to the blood stream of newborns or adult conditioned recipients, compared to the scarce vascular contribution of adult bone marrow cells. However, the specific SCL-PLAP(+) hematopoietic or endothelial cell subset responsible for the long-term reconstituting endothelial cell (LTR-EC) activity and its confinement to FL developmental stages remained unknown. Using a busulfan-treated newborn transplantation model, we show that LTR-EC activity is restricted to the SCL-PLAP(+) VE-cadherin(+) CD45(-) cell population, devoid of hematopoietic reconstitution activity and largely composed by Lyve1(+) endothelial-committed cells. SCL-PLAP(+) Ve-cadherin(+) CD45(-) cells contributed to the liver sinusoidal endothelium and also to the heart, kidney and lung microvasculature. LTR-EC activity was detected at different stages of FL development, yet marginal activity was identified in the adult liver, revealing unknown functional differences between fetal and adult liver endothelial/endothelial progenitors. Importantly, the observations that expanding donor-derived vascular grafts colocalize with proliferating hepatocyte-like cells and participate in the systemic circulation, support their functional integration into young livers. These findings offer new insights into the engraftment, phonotypical, and developmental characterization of a novel endothelial/endothelial progenitor cell subtype with multiorgan LTR-EC activity, potentially instrumental for the treatment/genetic correction of

  11. Maturation of long-term potentiation in the hippocampal dentate gyrus of the freely moving rat.

    PubMed

    Bronzino, J D; Abu-Hasaballah, K; Austin-LaFrance, R J; Morgane, P J

    1994-08-01

    The ability of the perforant path/dentate granule cell synapse of the hippocampal formation to establish and maintain enhanced levels of synaptic transmission in response to tetanization (long-term potentiation, LTP) was investigated in freely moving rats at 15, 30, and 90 days of age. Measures of 1) the slope of the population excitatory postsynaptic potential (EPSP), and 2) the population spike amplitude (PSA) obtained before, and at several times following tetanization, were used to evaluate the magnitude and duration of LTP as a function of age. Significant enhancement of both EPSP slope and PSA measures was obtained from animals of all three ages in response to perforant path tetanization. The initial degree of enhancement was essentially the same across the age groups, ranging from +27% to +38% of pretetanization levels for EPSP slope measures and +60% to +75% of pretetanization levels for PSA measures, obtained 15 min after tetanization. The duration of this enhancement obtained from animals of the preweaning group was significantly longer than that obtained from either 30- or 90-day-old animals. Enhanced measures of both EPSP slope and PSA decayed to baseline levels in these older animals 18 to 24 h after tetanization, while animals tetanized at 15 days of age maintained potentiated levels of both measures for a period of 5 days following tetanization. Tetanization of 15-day-old animals resulted in a significant reduction in the latency to EPSP onset without affecting the time-based relationships among the other measured parameters, which included latency of the population spike onset, population spike minimum, and population spike offset.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Ampakine CX717 potentiates intermittent hypoxia-induced hypoglossal long-term facilitation.

    PubMed

    Turner, S M; ElMallah, M K; Hoyt, A K; Greer, J J; Fuller, D D

    2016-09-01

    Glutamatergic currents play a fundamental role in regulating respiratory motor output and are partially mediated by α-amino-3-hydroxy-5-methyl-isoxazole-propionic acid (AMPA) receptors throughout the premotor and motor respiratory circuitry. Ampakines are pharmacological compounds that enhance glutamatergic transmission by altering AMPA receptor channel kinetics. Here, we examined if ampakines alter the expression of respiratory long-term facilitation (LTF), a form of neuroplasticity manifested as a persistent increase in inspiratory activity following brief periods of reduced O2 [intermittent hypoxia (IH)]. Current synaptic models indicate enhanced effectiveness of glutamatergic synapses after IH, and we hypothesized that ampakine pretreatment would potentiate IH-induced LTF of respiratory activity. Inspiratory bursting was recorded from the hypoglossal nerve of anesthetized and mechanically ventilated mice. During baseline (BL) recording conditions, burst amplitude was stable for at least 90 min (98 ± 5% BL). Exposure to IH (3 × 1 min, 15% O2) resulted in a sustained increase in burst amplitude (218 ± 44% BL at 90 min following final bout of hypoxia). Mice given an intraperitoneal injection of ampakine CX717 (15 mg/kg) 10 min before IH showed enhanced LTF (500 ± 110% BL at 90 min). Post hoc analyses indicated that CX717 potentiated LTF only when initial baseline burst amplitude was low. We conclude that under appropriate conditions ampakine pretreatment can potentiate IH-induced respiratory LTF. These data suggest that ampakines may have therapeutic value in the context of hypoxia-based neurorehabilitation strategies, particularly in disorders with blunted respiratory motor output such as spinal cord injury.

  13. Subcortical deafferentation impairs behavioral reinforcement of long-term potentiation in the dentate gyrus of freely moving rats.

    PubMed

    Almaguer-Melian, W; Rosillo, J C; Frey, J U; Bergado, J A

    2006-01-01

    Long-term potentiation is a form of neural functional plasticity which has been related with memory formation and recovery of function after brain injury. Previous studies have shown that a transient early-long-term potentiation can be prolonged by direct stimulation of distinct brain areas, or behavioral stimuli with a high motivational content. The basolateral amygdala and other subcortical structures, like the medial septum and the locus coeruleus, are involved in mediating the reinforcing effect. We have previously shown that the lesion of the fimbria-fornix--the main entrance of subcortical afferents to the hippocampus--abolishes the reinforcing basolateral amygdala-effects on long-term potentiation in the dentate gyrus in vivo. It remains to be investigated, however, if such subcortical afferents may also be important for behavioral reinforcement of long-term potentiation. Young-adult (8 weeks) Sprague-Dawley male rats were fimbria-fornix-transected under anesthesia, and electrodes were implanted at the dentate gyrus and the perforant path. One week after surgery the freely moving animals were studied. Fimbria-fornix-lesion reduced the ability of the animals to develop long-term potentiation when a short pulse duration was used for tetanization (0.1 ms per half-wave of a biphasic stimulus), whereas increasing the pulse duration to 0.2 ms per half-wave during tetanization resulted in a transient early-long-term potentiation lasting about 4 h in the lesioned animals, comparable to that obtained in non-lesioned or sham-operated control rats. In water-deprived (24 h) control animals, i.e. in non-lesioned and sham-operated rats, early-long-term potentiation could be behaviorally reinforced by drinking 15 min after tetanization. However, in fimbria-fornix-lesioned animals long-term potentiation-reinforcement by drinking was not detected. This result indicates that the effect of behavioral-motivational stimuli to reinforce long-term potentiation is mediated by

  14. Selective cholinergic depletion in medial septum leads to impaired long term potentiation and glutamatergic synaptic currents in the hippocampus.

    PubMed

    Kanju, Patrick M; Parameshwaran, Kodeeswaran; Sims-Robinson, Catrina; Uthayathas, Subramaniam; Josephson, Eleanor M; Rajakumar, Nagalingam; Dhanasekaran, Muralikrishnan; Suppiramaniam, Vishnu

    2012-01-01

    Cholinergic depletion in the medial septum (MS) is associated with impaired hippocampal-dependent learning and memory. Here we investigated whether long term potentiation (LTP) and synaptic currents, mediated by alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA) and N-methyl-D-aspartate (NMDA) receptors in the CA1 hippocampal region, are affected following cholinergic lesions of the MS. Stereotaxic intra-medioseptal infusions of a selective immunotoxin, 192-saporin, against cholinergic neurons or sterile saline were made in adult rats. Four days after infusions, hippocampal slices were made and LTP, whole cell, and single channel (AMPA or NMDA receptor) currents were recorded. Results demonstrated impairment in the induction and expression of LTP in lesioned rats. Lesioned rats also showed decreases in synaptic currents from CA1 pyramidal cells and synaptosomal single channels of AMPA and NMDA receptors. Our results suggest that MS cholinergic afferents modulate LTP and glutamatergic currents in the CA1 region of the hippocampus, providing a potential synaptic mechanism for the learning and memory deficits observed in the rodent model of selective MS cholinergic lesioning.

  15. Effects of prenatal protein malnutrition on hippocampal long-term potentiation in freely moving rats.

    PubMed

    Bronzino, J D; Austin-LaFrance, R J; Mokler, D; Morgane, P J

    1997-11-01

    It has been demonstrated that prenatal protein malnutrition significantly affects hippocampal plasticity, as measured by long-term potentiation, throughout development. This paper focuses on the hippocampal dentate granule cell population response to two separate paradigms of tetanization of the medial perforant pathway in prenatally protein-malnourished and normally nourished adult male rats. The 100-pulse paradigm consisted of the application of ten 25-ms-duration bursts of 400 Hz stimulation with an interburst interval of 10 s. The 1000-pulse paradigm consisted of the application of five 500-ms bursts of 400 Hz stimulation with an interburst interval of 5 s. No between-group differences were obtained for input/output response measures prior to tetanization. No between-group, nor between-paradigm, differences were obtained in the degree of population EPSP slope enhancement. However, in response to both paradigms, prenatally malnourished animals showed significantly less enhancement of the population spike amplitude (PSA) measure than normally nourished animals. Normally nourished animals showed a significantly greater level of PSA enhancement in response to the 100-pulse paradigm than the 1000-pulse paradigm. Prenatally malnourished animals showed no significant differences in the degree of PSA enhancement between the two paradigms. Results indicate that short duration bursts (< or = 25 ms) are more effective in inducing maximal PSA enhancement in normally nourished rats than longer duration stimulus bursts. The apparent inability of prenatally malnourished rats to transfer enhanced cellular activation (population EPSP slope enhancement) into enhanced cellular discharge (PSA enhancement) suggests that a preferential enhancement of GABAergic inhibitory modulation of granule cell excitability may result from the prenatal dietary insult. Such potentiation of inhibitory activity would significantly lower the probability of granule cell population discharge, resulting

  16. Antidepressants that inhibit both serotonin and norepinephrine reuptake impair long-term potentiation in hippocampus

    PubMed Central

    Cooke, Jennifer D.; Cavender, Hannah M.; Lima, Hope K.; Grover, Lawrence M.

    2014-01-01

    Rationale Monoamine reuptake inhibitors can stimulate expression of brain-derived neurotrophic factor (BDNF) and alter long-term potentiation (LTP), a widely used model for the synaptic mechanisms that underlie memory formation. BDNF expression is up-regulated during LTP, and BDNF in turn positively modulates LTP. Previously, we found that treatment with venlafaxine, a serotonin and norepinephrine reuptake inhibitor (SNRI), but not citalopram, a selective serotonin reuptake inhibitor (SSRI) reduced LTP in hippocampal area CA1 without changing hippocampal BDNF protein expression. Objectives We tested the hypothesis that combined serotonin and norepinephrine reuptake inhibition is necessary for LTP impairment, and we reexamined the potential role of BNDF by testing for region-specific changes in areas CA1, CA3 and dentate gyrus. We also tested whether early events in the LTP signaling pathway were altered to impair LTP. Methods Animals were treated for 21 days with venlafaxine, imipramine, fluoxetine, or maprotiline. In vitro hippocampal slices were used for electrophysiological measurements. Protein expression was measured by enzyme-linked immunosorbent assay (ELISA) and western blotting. Results LTP was impaired only following treatment with combined serotonin and norepinephrine reuptake inhibitors (venlafaxine, imipramine) but not with selective serotonin (fluoxetine) or norepinephrine (maprotiline) reuptake inhibitors. BDNF protein expression was not altered by venlafaxine or imipramine treatment, nor were postsynaptic depolarization during LTP inducing stimulation or synaptic membrane NMDA receptor subunit expression affected. Conclusions LTP is impaired by chronic treatment with antidepressant that inhibit both serotonin and norepinephrine reuptake; this impairment results from changes that are downstream of postsynaptic depolarization and calcium-influx. PMID:24781518

  17. In hippocampal oriens interneurons anti-Hebbian long-term potentiation requires cholinergic signaling via α7 nicotinic acetylcholine receptors.

    PubMed

    Griguoli, Marilena; Cellot, Giada; Cherubini, Enrico

    2013-01-16

    In the hippocampus, at excitatory synapses between principal cell and oriens/alveus (O/A) interneurons, a particular form of NMDA-independent long-term synaptic plasticity (LTP) has been described (Lamsa et al., 2007). This type of LTP occurs when presynaptic activation coincides with postsynaptic hyperpolarization. For this reason it has been named "anti-Hebbian" to distinguish from the classical Hebbian type of associative learning where presynaptic glutamate release coincides with postsynaptic depolarization. The different voltage dependency of LTP induction is thought to be mediated by calcium-permeable (CP) AMPA receptors that, due to polyamine-mediated rectification, favor calcium entry at hyperpolarized potentials. Here, we report that the induction of this form of LTP needs CP-α7 nicotinic acetylcholine receptors (nAChRs) that, like CP-AMPARs, exhibit a strong inward rectification because of polyamine block at depolarizing potentials. We found that high-frequency stimulation of afferent fibers elicits synaptic currents mediated by α7 nAChRs. Hence, LTP was prevented by α7 nAChR antagonists dihydro-β-erythroidine and methyllycaconitine (MLA) and was absent in α7(-/-) mice. In addition, in agreement with previous observations (Le Duigou and Kullmann, 2011), in a minority of O/A interneurons in MLA-treated hippocampal slices from WT animals and α7(-/-) mice, a form of LTP probably dependent on the activation of group I metabotropic glutamate receptors was observed. These data indicate that, in O/A interneurons, anti-Hebbian LTP critically depends on cholinergic signaling via α7 nAChR. This may influence network oscillations and information processing.

  18. A Model of Induction of Cerebellar Long-Term Depression Including RKIP Inactivation of Raf and MEK

    PubMed Central

    Hepburn, Iain; Jain, Anant; Gangal, Himanshu; Yamamoto, Yukio; Tanaka-Yamamoto, Keiko; De Schutter, Erik

    2017-01-01

    We report an updated stochastic model of cerebellar Long Term Depression (LTD) with improved realism. Firstly, we verify experimentally that dissociation of Raf kinase inhibitor protein (RKIP) from Mitogen-activated protein kinase kinase (MEK) is required for cerebellar LTD and add this interaction to an earlier published model, along with the known requirement of dissociation of RKIP from Raf kinase. We update Ca2+ dynamics as a constant-rate influx, which captures experimental input profiles accurately. We improve α-amino-3-hydroxy-5-methyl-4 isoxazolepropionic acid (AMPA) receptor interactions by adding phosphorylation and dephosphorylation of AMPA receptors when bound to glutamate receptor interacting protein (GRIP). The updated model is tuned to reproduce experimental Ca2+ peak vs. LTD amplitude curves at four different Ca2+ pulse durations as closely as possible. We find that the updated model is generally more robust with these changes, yet we still observe some sensitivity of LTD induction to copy number of the key signaling molecule Protein kinase C (PKC). We predict natural variability in this number by stochastic diffusion may influence the probabilistic LTD response to Ca2+ input in Purkinje cell spines and propose this as an extra source of stochasticity that may be important also in other signaling systems. PMID:28220061

  19. Mifepristone (RU486) inhibits lateral perforant path long-term potentiation in hippocampal slices from prenatally morphine-exposed female rats.

    PubMed

    Velísek, Libor; Vathy, Ilona

    2005-11-01

    In brain slices from prenatally saline-exposed female rats during proestrus and diestrus, long-term potentiation (LTP) can be induced in the lateral perforant pathway (LPP). Prenatal morphine exposure suppresses LTP induction in the LPP during proestrus. Here we studied synaptic plasticity in the LPP in slices from female rats prenatally exposed to morphine. Two additional factors were investigated: the role of the estrous cycle and role of glucocorticoid receptors. Hippocampal slices were prepared from adult, prenatally saline- or morphine-exposed female rats. One hour prior to decapitation, vaginal smears were obtained and the rats either in proestrus or diestrus were treated with a non-specific glucocorticoid receptor antagonist mifepristone (RU486) or with a vehicle. LPP was stimulated with high-frequency stimulation. Short-tem plasticity (STP) and the induction and maintenance of long-term potentiation (LTP) were assessed. In all groups of prenatally saline-exposed rats, LTP was induced and maintained with the exception of RU486-treated rats during proestrus where the LTP was induced but not maintained. In prenatally morphine-exposed females in diestrus, both STP and LTP were induced after postnatal vehicle treatment. In morphine-exposed, proestrous females, neither STP nor LTP were induced irrespective of the postnatal treatment. Thus, prenatal morphine exposure suppresses the induction of LTP in the LPP, except during diestrus. Data indicate that the induction and maintenance of LTP in the LPP in hippocampal slices from female rats is multifactorial: ovarian steroids and functionality of glucocorticoid receptors cooperation are necessary for induction and maintenance of the LTP, prenatal morphine exposure interferes with this process possibly by its long-term effects on synaptic plasticity.

  20. Minocycline Prevents the Impairment of Hippocampal Long-Term Potentiation in the Septic Mouse.

    PubMed

    Hoshino, Koji; Hayakawa, Mineji; Morimoto, Yuji

    2017-02-09

    Sepsis-associated encephalopathy is a major complication during sepsis, and an effective treatment remains unknown. Although minocycline (MINO) has neuroprotective effects and is an attractive candidate for treating sepsis-associated encephalopathy, the effect of MINO on synaptic plasticity during sepsis is still unclear. In the present study, we investigated the effects of MINO on long-term potentiation (LTP) in the hippocampus in a cecal ligation and puncture (CLP) mouse model. We divided mice into 4 groups; (1) sham + vehicle, (2) sham + MINO (60 mg/kg, i.p. for 3 consecutive days before slice preparation), (3) CLP + vehicle, and (4) CLP + MINO. We tested LTP in the CA1 region of the hippocampus, using slices taken 24 h after surgery. Because MINO is also anti-inflammatory, LTP was analyzed following 30 min of IL-1 receptor antagonist (IL-1ra) perfusion. The endotoxin level in the blood was increased at 24 h after CLP operations regardless of MINO administrations, and LTP in the CLP + vehicle group mice was severely impaired (P < 0.05). High doses of MINO prevented the LTP impairment during sepsis in the CLP + MINO group. Interleukin (IL) -1ra administration ameliorated LTP impairment only in the CLP + vehicle group (P < 0.05); it had no additional effects on LTP in the CLP + MINO group. In conclusion, we have provided the first evidence that MINO prevents impaired LTP related to sepsis-induced encephalopathy in the mouse hippocampus, and that mechanisms associated with IL-1 receptor activity may be involved.

  1. Sleep-Dependent Gene Expression in the Hippocampus and Prefrontal Cortex Following Long-Term Potentiation

    PubMed Central

    Romcy-Pereira, Rodrigo N.; Erraji-Benchekroun, Loubna; Smyrniotopoulos, Peggy; Ogawa, Sonoko; Mello, Claudio V.; Sibille, Etienne; Pavlides, Constantine

    2009-01-01

    The activity-dependent transcription factor zif268 is re-activated in sleep following hippocampal long-term potentiation (LTP). However, the activation of secondary genes, possibly involved in modifying local synaptic strengths and ultimately stabilizing memory traces during sleep, has not yet been studied. Here, we investigated changes in hippocampal and cortical gene expression at a time point subsequent to the previously reported initial zif268 re-activation during sleep. Rats underwent unilateral hippocampal LTP and were assigned to SLEEP or AWAKE groups. Eighty minutes after a long rapid-eye-movement sleep (REMS) episode (or an equivalent amount of time for awake group) animals had their hippocampi dissected and processed for gene microarray hybridization. Prefrontal and parietal cortices were also collected for qRT-PCR analysis. The microarray analysis identified 28 up-regulated genes in the hippocampus: 11 genes were enhanced in the LTPed hemisphere of sleep animals; 13 genes were enhanced after sleep, regardless of hemisphere; and 4 genes were enhanced in LTPed hemisphere, regardless of behavioral state. qRT-PCR analysis confirmed the upregulation of aif-1 and sc-65 during sleep. Moreover, we observed a down-regulation of the purinergic receptor, P2Y4R in the LTP hemisphere of awake animals and a trend for the protein kinase, CaMKI to be up-regulated in the LTP hemisphere of sleep animals. In the prefrontal cortex, we showed a significant LTP-dependent down-regulation of gluR1 and spinophilin specifically during sleep. Zif268 was downregulated in sleep regardless of the hemisphere. No changes in gene expression were observed in the parietal cortex. Our findings indicate that a set of synaptic plasticity-related genes have their expression modulated during sleep following LTP, which can reflect biochemical events associated with reshaping of synaptic connections in sleep following learning. PMID:19389414

  2. Cholecystokinin-octapeptide restored morphine-induced hippocampal long-term potentiation impairment in rats.

    PubMed

    Wen, Di; Zang, Guoqing; Sun, DongLei; Yu, Feng; Mei, Dong; Ma, Chunling; Cong, Bin

    2014-01-24

    Cholecystokinin-octapeptide (CCK-8), which is a typical brain-gut peptide, exerts a wide range of biological activities on the central nervous system. We have previously reported that CCK-8 significantly alleviated morphine-induced amnesia and reversed spine density decreases in the CA1 region of the hippocampus in morphine-treated animals. Here, we investigated the effects of CCK-8 on long-term potentiation (LTP) in the lateral perforant path (LPP)-granule cell synapse of rat dentate gyrus (DG) in acute saline or morphine-treated rats. Population spikes (PS), which were evoked by stimulation of the LPP, were recorded in the DG region. Acute morphine (30mg/kg, s.c.) treatment significantly attenuated hippocampal LTP and CCK-8 (1μg, i.c.v.) restored the amplitude of PS that was attenuated by morphine injection. Furthermore, microinjection of CCK-8 (0.1 and 1μg, i.c.v.) also significantly augmented hippocampal LTP in saline-treated (1ml/kg, s.c.) rats. Pre-treatment of the CCK2 receptor antagonist L-365,260 (10μg, i.c.v) reversed the effects of CCK-8, but the CCK1 receptor antagonist L-364,718 (10μg, i.c.v) did not. The present results demonstrate that CCK-8 attenuates the effect of morphine on hippocampal LTP through CCK2 receptors and suggest an ameliorative function of CCK-8 on morphine-induced memory impairment.

  3. The potential of Lake Karakul in the eastern Pamirs as a long-term climate archive

    NASA Astrophysics Data System (ADS)

    Mischke, S.; Rajabov, I.; Mustaeva, N.; Zhang, C.; Boomer, I.; Sherlock, S. C.; Myrbo, A.; Noren, A.; Brady, K.; Herzschuh, U.; Schudack, M. E.; Ito, E.

    2008-12-01

    Lake Karakul is a large closed-basin lake in the eastern Pamirs (NE Tajikistan) at an altitude of 3930 m. The lake fills a large basin about 45 km in diameter which may originate from a meteorite impact in the late Neogene. Exposed lake sediments at the northwestern shore 20 m above the lake display a bizarre Yardang relief indicating higher water levels in the past. Eroded remnants of lake, playa and fluvial sediments can be found on the northeastern slopes of the basin 200 m above the lake but their depositional age remains unknown. A field survey of the Lake Karakul region was conducted in July 2008 as a first attempt to evaluate the potential of the lake as a long-term climate archive in Central Asia. Sediment samples from the lake's bottom, water samples from the lake and inflowing streams, aquatic and terrestrial plant samples, and rock samples were collected to enable an interdisciplinary investigation of the lake and its catchment. A 1.04 m sediment core was obtained near the centre of the more shallow and flat eastern sub-basin of the lake at 19 m water depth. Corresponding to the lack of outlet and the resulting high pH (9.1) and electrical conductivity of the lake (10.3 mS/cm), fine aragonite needles constitute most of the sediments. Additionally, ostracod shells, aquatic plant fragments, detrital grains and Radix (Gastropoda) shells were recorded. First results of AMS 14C dating and ostracod analysis will be used to infer the environmental and climatic evolution of Lake Karakul in the Late Holocene.

  4. Activity-induced long-term potentiation of excitatory synapses in developing zebrafish retina in vivo.

    PubMed

    Wei, Hong-ping; Yao, Yuan-yuan; Zhang, Rong-wei; Zhao, Xiao-feng; Du, Jiu-lin

    2012-08-09

    Neural activity-induced long-term potentiation (LTP) of synaptic transmission is believed to be one of the cellular mechanisms underlying experience-dependent developmental refinement of neural circuits. Although it is well established that visual experience and neural activity are critical for the refinement of retinal circuits, whether and how LTP occurs in the retina remain unknown. Using in vivo perforated whole-cell recording and two-photon calcium imaging, we find that both repeated electrical and visual stimulations can induce LTP at excitatory synapses formed by bipolar cells on retinal ganglion cells in larval but not juvenile zebrafish. LTP induction requires the activation of postsynaptic N-methyl-D-aspartate receptors, and its expression involves arachidonic acid-dependent presynaptic changes in calcium dynamics and neurotransmitter release. Physiologically, both electrical and visual stimulation-induced LTP can enhance visual responses of retinal ganglion cells. Thus, LTP exists in developing retinae with a presynaptic locus and may serve for visual experience-dependent refinement of retinal circuits.

  5. Neonatal Tissue Damage Promotes Spike Timing-Dependent Synaptic Long-Term Potentiation in Adult Spinal Projection Neurons

    PubMed Central

    Li, Jie

    2016-01-01

    Mounting evidence from both humans and rodents suggests that tissue damage during the neonatal period can “prime” developing nociceptive pathways such that a subsequent injury during adulthood causes an exacerbated degree of pain hypersensitivity. However, the cellular and molecular mechanisms that underlie this priming effect remain poorly understood. Here, we demonstrate that neonatal surgical injury relaxes the timing rules governing long-term potentiation (LTP) at mouse primary afferent synapses onto mature lamina I projection neurons, which serve as a major output of the spinal nociceptive network and are essential for pain perception. In addition, whereas LTP in naive mice was only observed if the presynaptic input preceded postsynaptic firing, early tissue injury removed this temporal requirement and LTP was observed regardless of the order in which the inputs were activated. Neonatal tissue damage also reduced the dependence of spike-timing-dependent LTP on NMDAR activation and unmasked a novel contribution of Ca2+-permeable AMPARs. These results suggest for the first time that transient tissue damage during early life creates a more permissive environment for the production of LTP within adult spinal nociceptive circuits. This persistent metaplasticity may promote the excessive amplification of ascending nociceptive transmission to the mature brain and thereby facilitate the generation of chronic pain after injury, thus representing a novel potential mechanism by which early trauma can prime adult pain pathways in the CNS. SIGNIFICANCE STATEMENT Tissue damage during early life can “prime” developing nociceptive pathways in the CNS, leading to greater pain severity after repeat injury via mechanisms that remain poorly understood. Here, we demonstrate that neonatal surgical injury widens the timing window during which correlated presynaptic and postsynaptic activity can evoke long-term potentiation (LTP) at sensory synapses onto adult lamina I

  6. Opposing Actions of Chronic[Deta][superscript 9] Tetrahydrocannabinol and Cannabinoid Antagonists on Hippocampal Long-Term Potentiation

    ERIC Educational Resources Information Center

    Hoffman, Alexander F.; Oz, Murat; Yang, Ruiqin; Lichtman, Aron H.; Lupica, Carl R.

    2007-01-01

    Memory deficits produced by marijuana arise partly via interaction of the psychoactive component, [Deta][superscript 9]-tetrahydrocannabinol ([Deta][superscript 9]-THC), with cannabinoid receptors in the hippocampus. Although cannabinoids acutely reduce glutamate release and block hippocampal long-term potentiation (LTP), a potential substrate for…

  7. Hormonal and Monoamine Signaling during Reinforcement of Hippocampal Long-Term Potentiation and Memory Retrieval

    ERIC Educational Resources Information Center

    Korz, Volker; Frey, Julietta U.

    2007-01-01

    Recently it was shown that holeboard training can reinforce, i.e., transform early-LTP into late-LTP in the dentate gyrus during the initial formation of a long-term spatial reference memory in rats. The consolidation of LTP as well as of the reference memory was dependent on protein synthesis. We have now investigated the transmitter systems…

  8. Diet-induced alterations in the ontogeny of long-term potentiation.

    PubMed

    Bronzino, J D; Austin La France, R J; Morgane, P J; Galler, J R

    1996-01-01

    The ability of prenatally malnourished rats to establish and maintain long-term potentiation (LTP) of the perforant path/dentate granule cell synapse was examined in freely moving rats at 15, 30, and 90 days of age. Measures of the population EPSP slope and population spike amplitude (PSA) were calculated from dentate field potential recordings obtained prior to and at various times following tetanization of the perforant pathway. Significant enhancement of both population EPSP slope and PSA measures was obtained from all animals of both malnourished and well-nourished diet groups at 15 days of age. However, the magnitude of enhancement obtained from 15-day-old prenatally malnourished animals was significantly less than that of age-matched, well-nourished controls. At 30 days of age, PSA measures obtained from approximately 50% of prenatally malnourished 30-day-old rats showed no significant effect of tetanization, while measures obtained from the remaining 50% of these animals did not differ significantly from controls. EPSP slope measures for this age group followed much the same pattern, i.e., malnourished animals showing no significant enhancement of PSA measures exhibited only slight increases in EPSP slope beginning 1 h after tetanization and returned to baseline by 18 h post-tetanization. EPSP slope measures obtained from PSA-enhanced malnourished animals did not differ significantly from controls. At 90 days of age, PSA measures obtained from 50% of malnourished animals declined from pretetanization levels immediately following tetanization. Three hours after tetanization, however, this measure had increased to a level which did not differ significantly from that of the control group. PSA measures obtained from the remaining 50% of 90-day-old malnourished animals showed initial and sustained enhancement which did not differ significantly from those obtained from well-nourished age-matched controls. These results indicate that gestational protein

  9. Effects of exposure to an extremely low frequency electromagnetic field on hippocampal long-term potentiation in rat.

    PubMed

    Komaki, Alireza; Khalili, Afshin; Salehi, Iraj; Shahidi, Siamak; Sarihi, Abdolrahman

    2014-05-20

    Modern lifestyle exposes nearly all humans to electromagnetic fields, particularly to extremely low frequency electromagnetic fields (ELF-EMFs). Prolonged exposure to ELF-EMFs induces persistent changes in neuronal activity. However, the modulation of synaptic efficiency by ELF-EMFs in vivo is still unclear. In the present study, we investigated whether ELF-EMFs can change induction of long-term potentiation (LTP) and paired-pulse ratio (PPR) in the rat hippocampal area. Twenty-nine adult male Wistar rats were divided into 3 groups (ELF-EMF exposed, sham and control groups). The ELF-EMF group was exposed to a magnetic field for 90 consecutive days (2h/day). ELF-EMFs were produced by a circular coil (50Hz, 100 micro Tesla). The sham-exposed controls were placed in an identical chamber with no electromagnetic field. After this period, rats were deeply anesthetized with urethane (2.0mg/kg) and then a bipolar stimulating and recording electrode was implanted into the perforant pathway (PP) and dentate gyrus (DG), respectively. LTP in hippocampal area was induced by high-frequency stimulation (HFS). Prolonged exposure to ELF-EMFs increased LTP induction. There was a significant difference in the slope of EPSP and amplitude of PS between the ELF-EMF group and other groups. In conclusion, our data suggest that exposure to ELF-EMFs produces a marked change in the synaptic plasticity generated in synapses of the PP-DG. No significant difference in PPR of ELF-EMF group before and after HFS suggests a postsynaptic expression site of LTP.

  10. Long-Term Exercise Is a Potent Trigger for ΔFosB Induction in the Hippocampus along the dorso–ventral Axis

    PubMed Central

    Nishijima, Takeshi; Kawakami, Masashi; Kita, Ichiro

    2013-01-01

    Physical exercise improves multiple aspects of hippocampal function. In line with the notion that neuronal activity is key to promoting neuronal functions, previous literature has consistently demonstrated that acute bouts of exercise evoke neuronal activation in the hippocampus. Repeated activating stimuli lead to an accumulation of the transcription factor ΔFosB, which mediates long-term neural plasticity. In this study, we tested the hypothesis that long-term voluntary wheel running induces ΔFosB expression in the hippocampus, and examined any potential region-specific effects within the hippocampal subfields along the dorso–ventral axis. Male C57BL/6 mice were housed with or without a running wheel for 4 weeks. Long-term wheel running significantly increased FosB/ΔFosB immunoreactivity in all hippocampal regions measured (i.e., in the DG, CA1, and CA3 subfields of both the dorsal and ventral hippocampus). Results confirmed that wheel running induced region-specific expression of FosB/ΔFosB immunoreactivity in the cortex, suggesting that the uniform increase in FosB/ΔFosB within the hippocampus is not a non-specific consequence of running. Western blot data indicated that the increased hippocampal FosB/ΔFosB immunoreactivity was primarily due to increased ΔFosB. These results suggest that long-term physical exercise is a potent trigger for ΔFosB induction throughout the entire hippocampus, which would explain why exercise can improve both dorsal and ventral hippocampus-dependent functions. Interestingly, we found that FosB/ΔFosB expression in the DG was positively correlated with the number of doublecortin-immunoreactive (i.e., immature) neurons. Although the mechanisms by which ΔFosB mediates exercise-induced neurogenesis are still uncertain, these data imply that exercise-induced neurogenesis is at least activity dependent. Taken together, our current results suggest that ΔFosB is a new molecular target involved in regulating exercise

  11. Stimulus uncertainty enhances long-term potentiation-like plasticity in human motor cortex.

    PubMed

    Sale, Martin V; Nydam, Abbey S; Mattingley, Jason B

    2017-03-01

    Plasticity can be induced in human cortex using paired associative stimulation (PAS), which repeatedly and predictably pairs a peripheral electrical stimulus with transcranial magnetic stimulation (TMS) to the contralateral motor region. Many studies have reported small or inconsistent effects of PAS. Given that uncertain stimuli can promote learning, the predictable nature of the stimulation in conventional PAS paradigms might serve to attenuate plasticity induction. Here, we introduced stimulus uncertainty into the PAS paradigm to investigate if it can boost plasticity induction. Across two experimental sessions, participants (n = 28) received a modified PAS paradigm consisting of a random combination of 90 paired stimuli and 90 unpaired (TMS-only) stimuli. Prior to each of these stimuli, participants also received an auditory cue which either reliably predicted whether the upcoming stimulus was paired or unpaired (no uncertainty condition) or did not predict the upcoming stimulus (maximum uncertainty condition). Motor evoked potentials (MEPs) evoked from abductor pollicis brevis (APB) muscle quantified cortical excitability before and after PAS. MEP amplitude increased significantly 15 min following PAS in the maximum uncertainty condition. There was no reliable change in MEP amplitude in the no uncertainty condition, nor between post-PAS MEP amplitudes across the two conditions. These results suggest that stimulus uncertainty may provide a novel means to enhance plasticity induction with the PAS paradigm in human motor cortex. To provide further support to the notion that stimulus uncertainty and prediction error promote plasticity, future studies should further explore the time course of these changes, and investigate what aspects of stimulus uncertainty are critical in boosting plasticity.

  12. Exploring the Potential for Long-term Storage of Depleted Peridotite in the Mantle

    NASA Astrophysics Data System (ADS)

    Walter, M. J.; Parman, S.

    2006-12-01

    There is an increasingly powerful body of evidence indicating early, episodic extraction of material from the mantle during the Pre-Cambrian [e.g. 1,2]. These melt extraction events would inevitably have led to large- scale formation of depleted lithospheric mantle. Recent data from Helium and Osmium isotopic systems indicate an important role for ancient, depleted components in the mantle source regions of modern oceanic basalts [3,4]. The implication is that discrete fragments of ancient depleted lithosphere are stored in the mantle over long timescales, presumably through the mechanism of subduction. Melt extraction from fertile peridotite in the upper mantle yields a solid residue that ranges from depleted lherzolite to harzburgite or dunite. In the upper mantle the mineralogy of depleted peridotite is dominated by olivine and opx, and in the transition zone olivine undergoes polymorphic transitions and pyroxene converts to majorite. Depleted peridotite then transforms into an assemblage of Mg-perovskite and ferropericlase at about 670 km. For any given isotherm, depleted peridotite is less dense than fertile mantle throughout the upper mantle, and negative buoyancy can only occur in cold slabs. In the lower mantle depleted peridotite is enriched in ferropericlase relative to fertile mantle and recent experimental results indicate that KD (Pv/FP) may be a factor of 3 to 5 greater in fertile compositions than in depleted compositions, causing an increase in the Fe content of ferropericlase in depleted compositions. Whether or not discrete fragments of depleted peridotite can remain negatively buoyant in the deep mantle depends on many factors including temperature, the modal abundance of minerals and their relative compressibilities, and the amount of iron and its spin state in depleted and fertile lithologies. Here we present petrologic, geochemical and mineral physical modeling to investigate the potential for long-term storage of depleted peridotite as a

  13. Worldwide impact of aerosol's time scale on the predicted long-term concentrating solar power potential.

    PubMed

    Ruiz-Arias, Jose A; Gueymard, Christian A; Santos-Alamillos, Francisco J; Pozo-Vázquez, David

    2016-08-10

    Concentrating solar technologies, which are fuelled by the direct normal component of solar irradiance (DNI), are among the most promising solar technologies. Currently, the state-of the-art methods for DNI evaluation use datasets of aerosol optical depth (AOD) with only coarse (typically monthly) temporal resolution. Using daily AOD data from both site-specific observations at ground stations as well as gridded model estimates, a methodology is developed to evaluate how the calculated long-term DNI resource is affected by using AOD data averaged over periods from 1 to 30 days. It is demonstrated here that the use of monthly representations of AOD leads to systematic underestimations of the predicted long-term DNI up to 10% in some areas with high solar resource, which may result in detrimental consequences for the bankability of concentrating solar power projects. Recommendations for the use of either daily or monthly AOD data are provided on a geographical basis.

  14. Corticosterone Time-Dependently Modulates [beta]-Adrenergic Effects on Long-Term Potentiation in the Hippocampal Dentate Gyrus

    ERIC Educational Resources Information Center

    Pu, Zhenwei; Krugers, Harm J.; Joels, Marian

    2007-01-01

    Previous experiments in the hippocampal CA1 area have shown that corticosterone can facilitate long-term potentiation (LTP) in a rapid non-genomic fashion, while the same hormone suppresses LTP that is induced several hours after hormone application. Here, we elaborated on this finding by examining whether corticosterone exerts opposite effects on…

  15. The APP-Interacting Protein FE65 is Required for Hippocampus-Dependent Learning and Long-Term Potentiation

    ERIC Educational Resources Information Center

    Wang, Yan; Zhang, Ming; Moon, Changjong; Hu, Qubai; Wang, Baiping; Martin, George; Sun, Zhongsheng; Wang, Hongbing

    2009-01-01

    FE65 is expressed predominantly in the brain and interacts with the C-terminal domain of [beta]-amyloid precursor protein (APP). We examined hippocampus-dependent memory and in vivo long-term potentiation (LTP) at the CA1 synapses with isoform-specific FE65 knockout (p97FE65[superscript -/-]) mice. When examined using the Morris water maze,…

  16. Ethanol Acutely Inhibits Ionotropic Glutamate Receptor-mediated Responses and Long-Term Potentiation in the Developing CA1 Hippocampus

    PubMed Central

    Puglia, Michael P.; Valenzuela, C. Fernando

    2011-01-01

    Background Developmental ethanol (EtOH) exposure damages the hippocampus, causing long-lasting alterations in learning and memory. Alterations in glutamatergic synaptic transmission and plasticity may play a role in the mechanism of action of EtOH. This signaling is fundamental for synaptogenesis, which occurs during the third-trimester of human pregnancy (first 12 days of life in rats). Methods Acute coronal brain slices were prepared from 7–9 day-old rats. Extracellular and patch-clamp electrophysiological recording techniques were used to characterize the acute effects of EtOH on α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor (AMPAR)- and N-methyl-D-aspartate receptor (NMDAR)-mediated responses and long-term potentiation (LTP) in the CA1 hippocampal region. Results EtOH (40 and 80 mM) inhibited AMPAR- and NMDAR-mediated field excitatory postsynaptic potentials (fEPSPs). EtOH (80 mM) also reduced AMPAR-mediated fEPSPs in presence of an inhibitor of Ca2+ permeable AMPARs. The effect of 80 mM EtOH on NMDAR-mediated fEPSPs was significantly greater in presence of Mg2+. EtOH (80 mM) neither affected the paired-pulse ratio of AMPAR-mediated fEPSPs nor the presynaptic volley. The paired-pulse ratio of AMPAR-mediated excitatory postsynaptic currents was not affected either, and the amplitude of these currents was inhibited to a lesser extent than that of fEPSPs. EtOH (80 mM) inhibited LTP of AMPAR-mediated fEPSPs. Conclusions Acute EtOH exposure during the third-trimester equivalent of human pregnancy inhibits hippocampal glutamatergic transmission and LTP induction, which could alter synapse refinement and ultimately contribute to the pathophysiology of fetal alcohol spectrum disorder. PMID:20102565

  17. Deletion of CB2 cannabinoid receptors reduces synaptic transmission and long-term potentiation in the mouse hippocampus.

    PubMed

    Li, Yong; Kim, Jimok

    2016-03-01

    The effects of cannabinoids are mostly mediated by two types of cannabinoid receptors--CB1 receptors in the nervous system and CB2 receptors in the immune system. However, CB2 cannabinoid receptors have recently been discovered in the brain and also implicated in neurophysiological functions. The deletion of CB2 receptors in mice induces long-term memory deficits and schizophrenia-like behaviors, implying that endogenous activity of CB2 receptors might be involved in neuropsychiatric effects. Little is known about the cellular mechanisms by which physiological activation of CB2 receptors modulates neuronal functions. We aimed to determine how deletion of CB2 receptors in mice affects synaptic transmission and plasticity. Electrophysiological and morphological studies indicated that CB2 receptor knockout resulted in decreases in excitatory synaptic transmission, long-term potentiation, and dendritic spine density in the hippocampus. Our data imply that endogenous activity of CB2 receptors might contribute to the maintenance of synaptic functions and the expression of normal long-term potentiation. This study provides insights into the role of CB2 cannabinoid receptors in regulating cognitive functions such as long-term memory.

  18. Dynamics of nascent and active zone ultrastructure as synapses enlarge during long-term potentiation in mature hippocampus.

    PubMed

    Bell, Maria Elizabeth; Bourne, Jennifer N; Chirillo, Michael A; Mendenhall, John M; Kuwajima, Masaaki; Harris, Kristen M

    2014-12-01

    Nascent zones and active zones are adjacent synaptic regions that share a postsynaptic density, but nascent zones lack the presynaptic vesicles found at active zones. Here dendritic spine synapses were reconstructed through serial section electron microscopy (3DEM) and EM tomography to investigate nascent zone dynamics during long-term potentiation (LTP) in mature rat hippocampus. LTP was induced with theta-burst stimulation, and comparisons were made with control stimulation in the same hippocampal slices at 5 minutes, 30 minutes, and 2 hours post-induction and to perfusion-fixed hippocampus in vivo. Nascent zones were present at the edges of ∼35% of synapses in perfusion-fixed hippocampus and as many as ∼50% of synapses in some hippocampal slice conditions. By 5 minutes, small dense-core vesicles known to transport active zone proteins moved into more presynaptic boutons. By 30 minutes, nascent zone area decreased, without significant change in synapse area, suggesting that presynaptic vesicles were recruited to preexisting nascent zones. By 2 hours, both nascent and active zones were enlarged. Immunogold labeling revealed glutamate receptors in nascent zones; however, average distances from nascent zones to docked presynaptic vesicles ranged from 170 ± 5 nm in perfusion-fixed hippocampus to 251 ± 4 nm at enlarged synapses by 2 hours during LTP. Prior stochastic modeling suggests that decrease in glutamate concentration reduces the probability of glutamate receptor activation from 0.4 at the center of release to 0.1 just 200 nm away. Thus, conversion of nascent zones to functional active zones likely requires the recruitment of presynaptic vesicles during LTP.

  19. Total body irradiation causes long-term mouse BM injury via induction of HSC premature senescence in an Ink4a- and Arf-independent manner.

    PubMed

    Shao, Lijian; Feng, Wei; Li, Hongliang; Gardner, David; Luo, Yi; Wang, Yong; Liu, Lingbo; Meng, Aimin; Sharpless, Norman E; Zhou, Daohong

    2014-05-15

    Exposure to total body irradiation (TBI) induces not only acute hematopoietic radiation syndrome but also long-term or residual bone marrow (BM) injury. This residual BM injury is mainly attributed to permanent damage to hematopoietic stem cells (HSCs), including impaired self-renewal, decreased long-term repopulating capacity, and myeloid skewing. These HSC defects were associated with significant increases in production of reactive oxygen species (ROS), expression of p16(Ink4a) (p16) and Arf mRNA, and senescence-associated β-galacotosidase (SA-β-gal) activity, but not with telomere shortening or increased apoptosis, suggesting that TBI induces residual BM injury via induction of HSC premature senescence. This suggestion is supported by the finding that SA-β-gal(+) HSC-enriched LSK cells showed more pronounced defects in clonogenic activity in vitro and long-term engraftment after transplantation than SA-β-gal(-) LSK cells isolated from irradiated mice. However, genetic deletion of p16 and/or Arf had no effect on TBI-induced residual BM suppression and HSC senescence, because HSCs from irradiated p16 and/or Arf knockout (KO) mice exhibited changes similar to those seen in HSCs from wild-type mice after exposure to TBI. These findings provide important new insights into the mechanism by which TBI causes long-term BM suppression (eg, via induction of premature senescence of HSCs in a p16-Arf-independent manner).

  20. Long-term potentiation in rat hippocampal neurons is accompanied by spatially widespread changes in intrinsic oscillatory dynamics and excitability.

    PubMed

    Narayanan, Rishikesh; Johnston, Daniel

    2007-12-20

    Oscillations in neural activity are a prominent feature of many brain states. Individual hippocampal neurons exhibit intrinsic membrane potential oscillations and intrinsic resonance in the theta frequency range. We found that the subthreshold resonance frequency of CA1 pyramidal neurons was location dependent, varying more than 3-fold between the soma and the distal dendrites. Furthermore, activity- and NMDA-receptor-dependent long-term plasticity increased this resonance frequency through changes in h channel properties. The increase in resonance frequency and an associated reduction in excitability were nearly identical in the soma and the first 300 mum of the apical dendrites. These spatially widespread changes accompanying long-term synaptic potentiation also reduced the neuron's ability to elicit spikes evoked through a nonpotentiated synaptic pathway. Our results suggest that the frequency response of these neurons depends on the dendritic location of their inputs and that activity can regulate their response dynamics within an oscillating neural network.

  1. Inhibition of G9a/GLP Complex Promotes Long-Term Potentiation and Synaptic Tagging/Capture in Hippocampal CA1 Pyramidal Neurons.

    PubMed

    Sharma, Mahima; Razali, Nuralyah Bte; Sajikumar, Sreedharan

    2016-06-01

    Epigenetic regulations play an important role in regulating the learning and memory processes. G9a/G9a-like protein (GLP) lysine dimethyltransferase complex controls a prominent histone H3 lysine9 dimethylation (H3K9me2) that results in transcriptional silencing of the chromatin. Here, we report that the inhibition of G9a/GLP complex by either of the substrate competitive inhibitors UNC 0638 or BIX 01294 reinforces protein synthesis-independent long-term potentiation (early-LTP) to protein synthesis-dependent long-term potentiation (late-LTP). The reinforcement effect was observed if the inhibitors were present during the induction of early-LTP and in addition when G9a/GLP complex inhibition was carried out by priming of synapses within an interval of 30 min before or after the induction of early-LTP. Surprisingly, the reinforced LTP by G9a/GLP complex inhibition was able to associate with a weak plasticity event from nearby independent synaptic populations, resulting in synaptic tagging/capture (STC). We have identified brain-derived neurotrophic factor (BDNF) as a critical plasticity protein that maintains G9a/GLP complex inhibition-mediated LTP facilitation and its STC. Our study reveals an epigenetic mechanism for promoting plasticity and associativity by G9a/GLP complex inhibition, and it may engender a promising epigenetic target for enhancing memory in neural networks.

  2. Voluntary exercise rescues deficits in spatial memory and long-term potentiation in prenatal ethanol-exposed male rats.

    PubMed

    Christie, Brian R; Swann, Sarah E; Fox, Christopher J; Froc, David; Lieblich, Stephanie E; Redila, Van; Webber, Alina

    2005-03-01

    Prenatal ethanol exposure can lead to long-lasting impairments in the ability to process spatial information in rats, as well as produce long-lasting deficits in the ability of animals to exhibit long-term potentiation, a biological model of learning and memory processing. Conversely, we have recently shown that both spatial memory and long-term potentiation can be enhanced in animals that are given access to a running wheel in their home cage. In the present study, Sprague-Dawley rat dams were given one of three diets throughout gestation: (i) a liquid diet containing ethanol (35.5% ethanol-derived calories); (ii) a liquid diet, isocaloric to the ethanol diet, but with maltose-dextrin substituting for the ethanol derived calories and (iii) an ad libitum diet of standard rat chow. At weaning (28 days) animals were housed individually in either a standard rat cage, or a cage that contained a running wheel. Adult offspring were tested on a two trial version of the Morris water maze beginning at postnatal day 60, for five consecutive days. Following this, the capacity of the perforant path to dentate gyrus pathway to sustain long-term potentiation was examined in these animals using theta-patterned conditioning stimuli. Our results demonstrate that prenatal ethanol exposure can produce pronounced deficits in both spatial memory and long-term potentiation, but that allowing animal's access to voluntary exercise can attenuate these deficits to the point that those exposed to ethanol prenatally can no longer be differentiated from control animals. These findings indicate that voluntary exercise may have therapeutic benefits for individuals that have undergone prenatal ethanol exposure.

  3. Assessment of auditory evoked potential in long-term mobile phone users.

    PubMed

    Sevi, E Chandra; Kumar, P Sai; Mariam, Yasmin

    2014-01-01

    Mobile phones emit strong electromagnetic wave which causes structural and functional changes in the cell membrane within the central nervous system especially auditory system. The effect of duration of mobile phone use on auditory function was examined One hundred and seventy three long-term mobile phone users aged around 17-39 yrs (both male and female) were recruited in this study. The subjects were divided into three groups according to their age Group I (17-19 yrs), Group II (20-29 yrs), Group III (30-39 yrs). After getting informed consent the subjects were instructed to fill the questionnaire for the history related to our study, conduction deafness auditory brainstem response in both the ears were assessed. Significant difference was observed among three groups in their duration of mobile phone use. Latency of Waves in three groups showed significant difference. The average latency (both right and left ear) of waves I-V was found to be prolonged in Group II when compared to Group I and Group III. Interpeak latencies I-V and I-III showed differences among three groups. The findings of present study showed abnormalities in the conduction of electrical signals in different levels of auditory pathway.

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

    PubMed

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

    2011-12-14

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

  5. Sex Differences in Long-Term Potentiation at Temporoammonic-CA1 Synapses: Potential Implications for Memory Consolidation

    PubMed Central

    Xu, Ting; Yamaki, Vitor Nagai; Wei, Zhisheng; Huang, Mingfa; Rose, Gregory M.

    2016-01-01

    Sex differences in spatial memory have long been observed in humans, non-human primates and rodents, but the underlying cellular and molecular mechanisms responsible for these differences remain obscure. In the present study we found that adolescent male rats outperformed female rats in 7 d and 28 d retention probes, but not in learning trials and immediate probes, in the Morris water maze task. Male rats also had larger long-term potentiation (LTP) at hippocampal temproammonic-CA1 (TA-CA1) synapses, which have been implicated to play a key role in place field and memory consolidation, when protocols designed to elicit late-stage LTP (LLTP) were used. Interestingly, the ratio of evoked AMPA/NMDA currents was found to be smaller at TA-CA1 synapses in male rats compared to female rats. Protein biotinylation experiments showed that male rats expressed more surface GluN1 receptors in hippocampal CA1 stratum lacunosum-moleculare (SLM) than female rats, although GluA1 expression was also slightly higher in male rats. Taken together, our results suggest that differences in the expression of AMPA and NMDA receptors may affect LTP expression at TA-CA1 synapses in adolescent male and female rats, and thus possibly contribute to the observed sex difference in spatial memory. PMID:27806108

  6. Potential Role of Plasma Myeloperoxidase Level in Predicting Long-Term Outcome of Acute Myocardial Infarction

    PubMed Central

    Kaya, Mehmet Gungor; Yalcin, Ridvan; Okyay, Kaan; Poyraz, Fatih; Bayraktar, Nilufer; Pasaoglu, Hatice; Boyaci, Bulent; Cengel, Atiye

    2012-01-01

    We investigated the prognostic importance of plasma myeloperoxidase levels in patients with ST-elevation myocardial infarction (STEMI) at long-term follow-up, and we analyzed the correlations between plasma myeloperoxidase levels and other biochemical values. We evaluated 73 consecutive patients (56 men; mean age, 56 ±11 yr) diagnosed with acute STEMI and 46 age- and sex-matched healthy control participants. Patients were divided into 2 groups according to the median myeloperoxidase level (Group 1: plasma myeloperoxidase ≤68 ng/mL; and Group 2: plasma myeloperoxidase >68 ng/mL). Patients were monitored for the occurrence of major adverse cardiovascular events (MACE), which were defined as cardiac death; reinfarction; new hospital admission for angina; heart failure; and revascularization procedures. The mean follow-up period was 25 ± 16 months. Plasma myeloperoxidase levels were higher in STEMI patients than in control participants (82 ± 34 vs 20 ±12 ng/mL; P=0.001). Composite MACE occurred in 12 patients with high myeloperoxidase levels (33%) and in 4 patients with low myeloperoxidase levels (11%) (P=0.02). The incidences of nonfatal recurrent myocardial infarction and verified cardiac death were higher in the high-mye-loperoxidase group. In multivariate analysis, high plasma myeloperoxidase levels were independent predictors of MACE (odds ratio = 3.843; <95% confidence interval, 1.625–6.563; P=0.003). High plasma myeloperoxidase levels identify patients with a worse prognosis after acute STEMI at 2-year follow-up. Evaluation of plasma myeloperoxidase levels might be useful in determining patients at high risk of death and MACE who can benefit from further aggressive treatment and closer follow-up. PMID:22949765

  7. Potential role of plasma myeloperoxidase level in predicting long-term outcome of acute myocardial infarction.

    PubMed

    Kaya, Mehmet Gungor; Yalcin, Ridvan; Okyay, Kaan; Poyraz, Fatih; Bayraktar, Nilufer; Pasaoglu, Hatice; Boyaci, Bulent; Cengel, Atiye

    2012-01-01

    We investigated the prognostic importance of plasma myeloperoxidase levels in patients with ST-elevation myocardial infarction (STEMI) at long-term follow-up, and we analyzed the correlations between plasma myeloperoxidase levels and other biochemical values. We evaluated 73 consecutive patients (56 men; mean age, 56 ± 11 yr) diagnosed with acute STEMI and 46 age- and sex-matched healthy control participants. Patients were divided into 2 groups according to the median myeloperoxidase level (Group 1: plasma myeloperoxidase ≤ 68 ng/mL; and Group 2: plasma myeloperoxidase > 68 ng/mL). Patients were monitored for the occurrence of major adverse cardiovascular events (MACE), which were defined as cardiac death; reinfarction; new hospital admission for angina; heart failure; and revascularization procedures. The mean follow-up period was 25 ± 16 months. Plasma myeloperoxidase levels were higher in STEMI patients than in control participants (82 ± 34 vs 20 ± 12 ng/mL; P = 0.001). Composite MACE occurred in 12 patients with high myeloperoxidase levels (33%) and in 4 patients with low myeloperoxidase levels (11%) (P = 0.02). The incidences of nonfatal recurrent myocardial infarction and verified cardiac death were higher in the high-myeloperoxidase group. In multivariate analysis, high plasma myeloperoxidase levels were independent predictors of MACE (odds ratio = 3.843; <95% confidence interval, 1.625-6.563; P = 0.003). High plasma myeloperoxidase levels identify patients with a worse prognosis after acute STEMI at 2-year follow-up. Evaluation of plasma myeloperoxidase levels might be useful in determining patients at high risk of death and MACE who can benefit from further aggressive treatment and closer follow-up.

  8. In vivo expression of ganglionic long-term potentiation in superior cervical ganglia from hypertensive aged rats.

    PubMed

    Alzoubi, K H; Aleisa, A M; Alkadhi, K A

    2010-05-01

    Sustained increase in central sympathetic outflow to ganglia may provide the repeated high frequency presynaptic activity required for induction of long-term potentiation in sympathetic ganglia (gLTP), which is known to be involved in the manifestation of a neurogenic form of hypertension, namely stress-hypertension. Aging is often viewed as a progressive decline in physiological competence with a corresponding impaired ability to adapt to stressful stimuli. Old animals have exaggerated sympathetic activity as well as increased morbidity and mortality during prolonged exposure to stressful stimuli. Using the superior cervical ganglion (SCG) as a model for sympathetic ganglia, electrophysiological and biochemical evidence show that mildly hypertensive aged rats (22-month old) have expressed gLTP in vivo. This is suggested by a number of lines of evidence. Firstly, a shift in input/output (I/O) curve of ganglia from aged rats to the left side of I/O curve of ganglia from 6-month old (adult) rats indicating expression of gLTP. Secondly, failure of in vitro high frequency stimulation to induce gLTP in ganglia isolated from aged rats, which indicates occlusion due to saturation, which, in turn, suggests in vivo expression of gLTP in these ganglia. Thirdly, in vitro inhibition of basal ganglionic transmission by blockers of gLTP (5-HT(3) antagonists) is observed in ganglia isolated from aged rats, but not in those from adult rats. Finally, immunoblot analysis revealed that protein levels of signaling molecules such as calcium-calmodulin kinase II (CaMKII; phosphorylated and total), which normally increase during expression of LTP, are elevated in ganglia isolated from aged rats compared to those from adult ones. Protein levels of calcineurin, which dephosphorylates P-CaMKII, were reduced in ganglia isolated from aged rats, probably as a support mechanism to allow prolonged phosphorylation of CaMKII. Our findings suggest in vivo expression of gLTP in sympathetic ganglia

  9. Long term impact of different tillage practices on soil C sequestration potential

    NASA Astrophysics Data System (ADS)

    Valboa, Giuseppe; Lagomarsino, Alessandra; Papini, Rossella; Brandi, Giorgio; Elio Agnelli, Alessandro; Simoncini, Stefania; Vignozzi, Nadia; Pellegrini, Sergio

    2013-04-01

    Long-term experiments provide important information on the impact of agricultural management practices on soil quality. In 1994, a trial was started to investigate the effects of four different tillage systems on organic carbon and physical properties of a Calcari Fluvic Cambisol loam soil under continuous maize. The tillage practices compared were: conventional tillage by mould-board ploughing to 40 cm depth (DP); ripper sub-soiling to 40-45 cm (RS); shallow tillage by mould-board ploughing to 20 cm depth (SP); minimum tillage by disk harrowing to 10-15 cm (DH). Soil carbon pool, bulk density, macroporosity and aggregate stability were studied at different depth increments (0-10, 10-20, 20-30 and 30-40 cm) and by two repeated samplings (in 1999 and 2011), in order to evaluate their temporal evolution under the different tillage systems. For a better understanding of mechanisms leading to C sequestration, a qualitative characterization of soil organic matter (OM) was performed by acid hydrolysis (HCl 6N), in order to separate the labile and the recalcitrant fractions. After 18 years of treatments we hypothesized changes in OM content and quality, as well as in its vertical distribution, due to tillage practices. At the end of the trial, soil total organic carbon (TOC) stock increased in the surface layers under DH (to 10 cm depth), RS (to 20 cm depth) and SP (to 10 cm depth), while it was unchanged under DP. When considering the whole 0-40 cm layer, all tillage treatments resulted in no significant variation in TOC stock. OM quality and its evolution over time showed well defined differences among treatments: the OM recalcitrant fraction increased under RS (up to 30 cm depth), decreased under DP (up to 40 cm depth) and showed no significant changes under DH and SP. The negative impact of DP on C stabilization was confirmed by a significant decrease of the recalcitrant to TOC ratio in the whole sampled layer. In conclusion, DP showed the worst impact on C storage

  10. Activation of presynaptic and postsynaptic ryanodine-sensitive calcium stores is required for the induction of long-term depression at GABAergic synapses in the neonatal rat hippocampus.

    PubMed

    Caillard, O; Ben-Ari, Y; Gaïarsa, J L

    2000-09-01

    The role of internal calcium stores in the induction of long-term depression at GABAergic synapses was investigated in the neonatal rat hippocampus. Whole-cell recordings of CA3 pyramidal neurons were performed on hippocampal slices from neonatal (2-4 d old) rats. In control conditions, tetanic stimulation (TS) evoked an NMDA-dependent long-term depression of GABA(A) receptor-mediated postsynaptic responses (LTD(GABA-A)). LTD(GABA-A) was prevented when the cells were loaded with ruthenium red, a blocker of Ca2+-induced Ca2+ release (CICR) stores, whereas loading the cells with heparin, a blocker of IP3-induced Ca2+ release stores, had no effect. The effects of ryanodine, another compound that interferes with CICR stores, were also investigated. Intracellular injection of ryanodine prevented the induction of LTD(GABA-A) only when the TS was preceded by depolarizing pulses that increase intracellular Ca2+ concentration. When applied in the bath, ryanodine prevented the induction of LTD(GABA-A). Altogether, these results suggest that ryanodine acts as a Ca2+-dependent blocker of CICR stores and that the induction of LTD(GABA-A) required the activation of both presynaptic and postsynaptic CICR stores.

  11. The timing of maternal separation affects morris water maze performance and long-term potentiation in male rats.

    PubMed

    Cao, Xiujing; Huang, Shenghai; Cao, Jiejie; Chen, Tingting; Zhu, Ping; Zhu, Rui; Su, Puyu; Ruan, Diyun

    2014-07-01

    The increasing evidences showed that adverse early life events have profound long lasting consequences in adult rats including neural, behavioral, and cognitive effects. Early maternal separation was one of the models of adverse early life stress, but which period acts critically was unknown until now. The purpose of this paper was to explore the effects of maternal separation in different periods, that is, postnatal Day 2-9 and postnatal Day 14-21, on spatial learning and memory and long-term potentiation (LTP) in hippocampus of adolescent rats. Rat pups were assigned to three groups: early maternal separation from postnatal Day 2-9 (EMS2-9), separation from postnatal Day 14-21 (EMS14-21), and control (Con)--rats stayed with their mother all the time before weaning. Morris water maze test (MWM) and electrophysiological test were performed at 40-50 days of age. The results indicated that EMS14-21 impaired spatial learning and memory ability. For the excitatory postsynaptic potential long-term potentiation (EPSP LTP), both the two maternal separation groups showed decreased values compared to control group. In terms of population spike long-term potentiation (PS LTP), both the two maternal separation groups also showed lower values compared with control group, but only EMS14-21 group had significant difference compared with control group. In conclusion, our results revealed that EMS14-21 showed worst in both escape latency in Morris Water Maze test and LTP compared to control group and EMS2-9 group.

  12. Long-Term Fatigue Life Expenditure of Turbine Shafts Owing to Noncharacteristic Harmonics Produced by Slip Energy Recovery Induction Motor Drives

    NASA Astrophysics Data System (ADS)

    Tsai, Jong-Ian

    In this paper, the long-term effect of noncharacteristic harmonics resulting from a slip energy recovery induction motor drive (SERIMD) on the fatigue life expenditure of turbine-generator shafts is analyzed. A feed-water pump (FP) in power plants is one of the most essential pieces of auxiliary equipment and consumes considerably large quantities of energy. An SERIMD has many advantages and is an adequate candidate for the purpose of variable speed control. However, it gives rise to sustainable variable frequency subharmonics which induce electromechanical subsynchronous oscillations in turbine shafts through proposed deductions. Accordingly, the author has determined that the long-term effect of these subharmonics is a cause of fatigue damage on turbine shafts even under normal operating conditions through fatigue life estimation.

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

    SciTech Connect

    Chen, P.-Y.; Huang, Lynn L.H. . E-mail: lynn@mail.ncku.edu.tw; Hsieh, H.-J. . E-mail: hjhsieh@ntu.edu.tw

    2007-08-17

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

  14. Ryanodine produces a low frequency stimulation-induced NMDA receptor-independent long-term potentiation in the rat dentate gyrus in vitro.

    PubMed Central

    Wang, Y; Wu, J; Rowan, M J; Anwyl, R

    1996-01-01

    1. The induction of long-term potentiation (LTP) was investigated in the rat dentate gyrus in the presence of ryanodine, an agent which is known to selectively bind to the ryanodine receptor (RyR) Ca2+ channels which regulate Ca2+ release from intracellular Ca2+ stores. 2. In control media, high frequency stimulation (HFS) induced LTP, and prolonged low frequency stimulation (LFS) induced long-term depression (LTD), of field excitatory postsynaptic potentials (EPSPs) and patch clamped excitatory postsynaptic currents (EPSCs). 3. In the presence of ryanodine, at a threshold concentration of about 1 microM, HFS-induced LTP was inhibited, whereas LFS (5 Hz, 900 pulses) now induced LTP. 4. The N-methyl-D-aspartate receptor (NMDAR) antagonist D-2-amino-phosphonopentanoate (D-AP5), at both 50 and 200 microM, did not prevent the induction of LTP by 5 Hz LFS in the presence of ryanodine. This demonstrates the NMDAR independence of LTP induction in the presence of ryanodine. Furthermore, D AP5 reversed the block of HFS-induced LTP by ryanodine. 5. The induction of LTP by 5 Hz LFS in the presence of ryanodine was blocked by lowering extracellular Ca2+, or by rapidly buffering intracellular Ca2+ to very low levels with BAPTA. 6. The induction of LTP by 5 Hz LFS was inhibited by the L-type voltage-gated Ca2+ channel blocker nifedipine, and also by Ni2+ a commonly used T type voltage-gated Ca2+ channel blocker. 7. The 5 Hz LFS-induced LTP in the presence of ryanodine was inhibited by the metabotropic glutamate receptor (mGluR) antagonist (+)-alpha-methyl 4-carboxyphenylglycine (MCPG). 8. The 5 Hz LFS-induced LTP in the presence of ryanodine was blocked by Ruthenium Red, an agent known to block RyR channel opening, and also by thapsigargin, an agent known to block-ATP-dependent Ca2+ uptake into endoplasmic reticulum. 9. The results of the present studies emphasize the importance of intracellular Ca2+ stores in the induction of LTP. PMID:8887781

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

    PubMed Central

    Lenz, Maximilian; Vlachos, Andreas; Maggio, Nicola

    2015-01-01

    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. PMID:26692832

  16. Potential for long-term LNG supplies to the United States

    SciTech Connect

    Lihn, M.L.

    1992-02-01

    Topics discussed here include: (1) terminal capacity; (2) potential sources for US LNG (liquefied natural gas) imports; (3) LNG liquefaction and transportation capacity; (4) historical US LNG imports; (5) LNG supply costs; (6)delivered cost of future LNG imports.

  17. Long-term potentiation in freely moving rats reveals asymmetries in thalamic and cortical inputs to the lateral amygdala.

    PubMed

    Doyère, Valérie; Schafe, Glenn E; Sigurdsson, Torfi; LeDoux, Joseph E

    2003-06-01

    Long-term memory underlying Pavlovian fear conditioning is believed to involve plasticity at sensory input synapses in the lateral nucleus of the amygdala (LA). A useful physiological model for studying synaptic plasticity is long-term potentiation (LTP). LTP in the LA has been studied only in vitro or in anaesthetized rats. Here, we tested whether LTP can be induced in auditory input pathways to the LA in awake rats, and if so, whether it persists over days. In chronically implanted rats, extracellular field potentials evoked in the LA by stimulation of the auditory thalamus and the auditory association cortex, using test simulations and input/output (I/O) curves, were compared in the same animals after tetanization of either pathway alone or after combined tetanization. For both pathways, LTP was input-specific and long lasting. LTP at cortical inputs exhibited the largest change at early time points (24 h) but faded within 3 days. In contrast, LTP at thalamic inputs, though smaller initially than cortical LTP, remained stable until at least 6 days. Comparisons of I/O curves indicated that the two pathways may rely on different mechanisms for the maintenance of LTP and may benefit differently from their coactivation. This is the first report of LTP at sensory inputs to the LA in awake animals. The results reveal important characteristics of synaptic plasticity in neuronal circuits of fear memory that could not have been revealed with in vitro preparations, and suggest a differential role of thalamic and cortical auditory afferents in long-term memory of fear conditioning.

  18. Assessment of the potential for long-term toxicological effects of the Exxon Valdez oil spill on birds and mammals

    SciTech Connect

    Hartung, R.

    1995-12-31

    This paper assesses the potential for direct long-term toxicological effects of exposures to oils in birds and mammals by tracing exposures and effects form the initial cute phases through the sub-chronic to the eventual long-term exposures. The immediate effects of oil spills are physical, the oil acting on the plumage of birds or the fur of mammals. This causes a loss of entrained air and a concomitant reduction in buoyancy and thermal insulation. Animals that escape the immediate impacts may be isolated from their food supply and often ingest large amounts of oil while attempting to clean themselves. At the comparatively high dose levels involved, these exposures can result in toxicologically significant responses in many organ systems. In the course of an oil pollution incident, the amounts of biologically available oils decrease steadily, and simultaneously the composition of the oils shifts towards those components that have low volatility, and that resist photo- and bio-degradation. As this occurs, the primary pathways of exposure change from direct intakes to indirect routes involving the food supply. Although laboratory studies often report finding some adverse effects, the dose rates employed in many of these studies are extremely high when compared with those that are potentially available to animals in the wild, and very few actually use weathered oils. An assessment of the toxicological literature and of the available empirical data on the Exxon Valdez oil spill leads to the conclusion that long-term sub-lethal toxic effects of crude oils on wildlife in such marine spills appear to be very unlikely. 111 refs., 4 figs., 1 tab.

  19. Differential effects of pentylenetetrazol-kindling on long-term potentiation of population excitatory postsynaptic potentials and population spikes in the CA1 region of rat hippocampus.

    PubMed

    Palizvan, M R; Fathollahi, Y; Semnanian, S; Hajezadeh, S; Mirnajafizadh, J

    2001-04-13

    The effects of pentylenetetrazol-kindling on synaptic transmission and the effectiveness of θ pattern primed-bursts (PBs) for the induction of long-term potentiation (LTP) of population excitatory postsynaptic potentials and population spikes were investigated in hippocampal CA1 of pentylenetetrazol-kindled rats. Experiments were carried out in the control and kindled animals at two post-kindling periods, i.e., 48-144 h (early phase) and 30-33 days (long lasting phase). Field potentials (population excitatory postsynaptic potentials, pEPSPs; and population spikes, PSs) were recorded at the stratum radiatum and the stratum pyramidale following stimulation of the stratum fibers, respectively. PBs were delivered to stratum fibers and PB potentiation was assessed. The results showed that 48-144 h after kindling there was no significant difference for pEPSP slope and PS amplitude between two groups. But at 30-33 days after kindling, the pEPSP slope in the stratum radiatum of kindled animals decreased, whereas the amplitude of PSs increased compared to those of controls. Shortly after kindling, control animals had normal LTP of pEPSP slope and PS amplitude in response to PBs, but kindled rats lack LTP of pEPSP slope and PBs induced LTP of PS amplitude in most of kindled animals. In 30-33 days after kindling, PB potentiation was not observed in the stratum radiatum of kindled animals but PBs induced LTP of PS amplitude, which was significantly greater than that of control animals. The effect is compatible with the hypothesis, which postulates kindling-associated functional deficit in hippocampus, especially CA1, as an explanation for the behavioral deficits seen with the kindling model of epilepsy.

  20. Regional prediction of long-term landfill gas to energy potential.

    PubMed

    Amini, Hamid R; Reinhart, Debra R

    2011-01-01

    Quantifying landfill gas to energy (LFGTE) potential as a source of renewable energy is difficult due to the challenges involved in modeling landfill gas (LFG) generation. In this paper a methodology is presented to estimate LFGTE potential on a regional scale over a 25-year timeframe with consideration of modeling uncertainties. The methodology was demonstrated for the US state of Florida, as a case study, and showed that Florida could increase the annual LFGTE production by more than threefold by 2035 through installation of LFGTE facilities at all landfills. The estimated electricity production potential from Florida LFG is equivalent to removing some 70 million vehicles from highways or replacing over 800 million barrels of oil consumption during the 2010-2035 timeframe. Diverting food waste could significantly reduce fugitive LFG emissions, while having minimal effect on the LFGTE potential; whereas, achieving high diversion goals through increased recycling will result in reduced uncollected LFG and significant loss of energy production potential which may be offset by energy savings from material recovery and reuse. Estimates showed that the power density for Florida LFGTE production could reach as high as 10 Wm(-2) with optimized landfill operation and energy production practices. The environmental benefits from increased lifetime LFG collection efficiencies magnify the value of LFGTE projects.

  1. Thyroid-stimulating hormone (TSH)-directed induction of the CREM gene in the thyroid gland participates in the long-term desensitization of the TSH receptor.

    PubMed Central

    Lalli, E; Sassone-Corsi, P

    1995-01-01

    Thyroid gland function is regulated by the hypothalamic-pituitary axis via the secretion of TSH, according to environmental, developmental, and circadian stimuli. TSH modulates both the secretion of thyroid hormone and gland trophism through interaction with a specific guanine nucleotide-binding protein-coupled receptor (TSH receptor; TSH-R), which elicits the activation of the cAMP-dependent signaling pathway. After TSH stimulation, the levels of TSH-R RNA are known to decrease dramatically within a few hours. This phenomenon ultimately leads to homologous long-term desensitization of the TSH-R. Here we show that TSH drives the induction of the inducible cAMP early repressor (ICER) isoform of the cAMP response element (CRE) modulator gene both in rat thyroid gland and in the differentiated thyroid cell line FRTL-5. The kinetics of ICER protein induction mirrors the down-regulation of TSH-R mRNA. ICER binds to a CRE-like sequence in the TSH-R promoter and represses its expression. Thus, ICER induction by TSH in the thyroid gland represents a paradigm of the molecular mechanism by which pituitary hormones elicit homologous long-term desensitization. Images Fig. 1 Fig. 2 Fig. 3 PMID:7568187

  2. Potentially mineralizable nitrogen as a soil health indicator in a Long-Term Agroecosystem Research site

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Potentially mineralizable nitrogen (PMN) has demonstrated utility as a valuable soil health indicator. However, the relationship between the total PMN pool and nitrogen mineralization rates has not been well described. A better understanding of PMN dynamics in agroecosystems is essential for optimiz...

  3. Dakota Diamond: An exceptionally high yielding, cold chipping potato cultivar with long-term storage potential

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Dakota Diamond (ND5822C-7) is a medium to late maturing cultivar with uniformly sized tubers and very high yield potential. It resulted from the cross of ND4103-2 and “Dakota Pearl”. Dakota Diamond is comprised of approximately 23.3% wild potato species germplasm. It combines the characteristics ...

  4. Potential for assessing long-term dynamics in soil nitrogen availability from variations in delta15N of tree rings.

    PubMed

    Hart, S C; Classen, A T

    2003-03-01

    Numerous researchers have used the isotopic signatures of C, H, and O in tree rings to provide a long-term record of changes in the physiological status, climate, or water-source use of trees. The frequently limiting element N is also found in tree rings, and variation in its isotopic signature may provide insight into long-term changes in soil N availability of a site. However, research has suggested that N is readily translocated among tree ring of different years; such infidelity between the isotopic compositions of the N taken up from the soil and the N contained in the ring of that growth year would obscure the long-term N isotopic record. We used a 15-year 15N-tracer study to assess the degree of N translocation among tree rings in ponderosa pine (Pinus ponderosa) trees growing in a young, mixed-conifer plantation. We also measured delta13C and delta15N values in unlabeled trees to assess the degree of their covariance in wood tissue, and to explore the potential for a biological linkage between them. We found that the maximum delta15N values in rings from the labeled trees occurred in the ring formed one-year after the 15N was applied to the roots. The delta15N value of rings from labeled trees declined exponentially and bidirectionally from this maximum peak, toward younger and older rings. The unlabeled trees showed considerable interannual variation in the delta15N values of their rings (up to 3 and 5 per thousand), but these values correlated poorly between trees over time and differed by as much as 6 per thousand. Removal of extractives from the wood reduced their delta15N value, but the change was fairly small and consistent among unlabeled trees. The delta13C and delta15N values of tree rings were correlated over time in only one of the unlabeled trees. Across all trees, both delta13C values of tree rings and annual stem wood production were well correlated with annual precipitation, suggesting that soil water balance is an important environmental

  5. The Long-Term Market Potential of Concentrating Solar Power (CSP) Systems

    SciTech Connect

    Smith, Steven J.

    2012-10-30

    This chapter will examine the conditions under which thermal CSP systems might play a large role in the global energy system. CSP technologies, such as troughs or power towers, have a large advantage over other solar technologies in that they offer the potential for firm power delivery, mitigating intermittency issues. These systems require relatively cloud-free conditions to operate, which limits their geographic applicability.

  6. Ampakines promote spine actin polymerization, long-term potentiation, and learning in a mouse model of Angelman syndrome.

    PubMed

    Baudry, Michel; Kramar, Eniko; Xu, Xiaobo; Zadran, Homera; Moreno, Stephanie; Lynch, Gary; Gall, Christine; Bi, Xiaoning

    2012-08-01

    Angelman syndrome (AS) is a neurodevelopmental disorder largely due to abnormal maternal expression of the UBE3A gene leading to the deletion of E6-associated protein. AS subjects have severe cognitive impairments for which there are no therapeutic interventions. Mouse models (knockouts of the maternal Ube3a gene: 'AS mice') of the disorder have substantial deficits in long-term potentiation (LTP) and learning. Here we report a clinically plausible pharmacological treatment that ameliorates both deficits. AS mice were injected ip twice daily for 5 days with vehicle or the ampakine CX929; drugs of this type enhance fast EPSCs by positively modulating AMPA receptors. Theta burst stimulation (TBS) produced a normal enhancement of field EPSPs in hippocampal slices prepared from vehicle-treated AS mice but LTP decreased steadily to baseline; however, LTP in slices from ampakine-treated AS mice stabilized at levels found in wild-type controls. TBS-induced actin polymerization within dendritic spines, an essential event for stabilizing LTP, was severely impaired in slices from vehicle-treated AS mice but not in those from ampakine-treated AS mice. Long-term memory scores in a fear conditioning paradigm were reduced by 50% in vehicle-treated AS mice but were comparable to values for littermate controls in the ampakine-treated AS mice. We propose that AS is associated with a profound defect in activity-driven spine cytoskeletal reorganization, resulting in a loss of the synaptic plasticity required for the encoding of long-term memory. Notably, the spine abnormality along with the LTP and learning impairments can be reduced by a minimally invasive drug treatment.

  7. SAMP8 mice have altered hippocampal gene expression in long term potentiation, phosphatidylinositol signaling, and endocytosis pathways.

    PubMed

    Armbrecht, Harvey J; Siddiqui, Akbar M; Green, Michael; Farr, Susan A; Kumar, Vijaya B; Banks, William A; Patrick, Ping; Shah, Gul N; Morley, John E

    2014-01-01

    The senescence-accelerated mouse (SAMP8) strain exhibits decreased learning and memory and increased amyloid beta (Aβ) peptide accumulation at 12 months. To detect differences in gene expression in SAMP8 mice, we used a control mouse that was a 50% cross between SAMP8 and CD-1 mice and which showed no memory deficits (50% SAMs). We then compared gene expression in the hippocampus of 4- and 12-month-old SAMP8 and control mice using Affymetrix gene arrays. At 12 months, but not at 4 months, pathway analysis revealed significant differences in the long term potentiation (6 genes), phosphatidylinositol signaling (6 genes), and endocytosis (10 genes) pathways. The changes in long term potentiation included mitogen-activated protein kinase (MAPK) signaling (N-ras, cAMP responsive element binding protein [CREB], protein phosphatase inhibitor 1) and Ca-dependent signaling (inositol triphosphate [ITP] receptors 1 and 2 and phospholipase C). Changes in phosphatidylinositol signaling genes suggested altered signaling through phosphatidylinositol-3-kinase, and Western blotting revealed phosphorylation changes in serine/threonine protein kinase AKT and 70S6K. Changes in the endocytosis pathway involved genes related to clathrin-mediated endocytosis (dynamin and clathrin). Endocytosis is required for receptor recycling, is involved in Aβ metabolism, and is regulated by phosphatidylinositol signaling. In summary, these studies demonstrate altered gene expression in 3 SAMP8 hippocampal pathways associated with memory formation and consolidation. These pathways might provide new therapeutic targets in addition to targeting Aβ metabolism itself.

  8. Cannabinoid CB1 receptor deficiency increases contextual fear memory under highly aversive conditions and long-term potentiation in vivo.

    PubMed

    Jacob, Wolfgang; Marsch, Rudolph; Marsicano, Giovanni; Lutz, Beat; Wotjak, Carsten T

    2012-07-01

    The cannabinoid receptor type 1 (CB1) is abundantly expressed in the central nervous system where it negatively controls the release of several neurotransmitters. CB1 activity plays a crucial role in learning and memory and in synaptic plasticity. In the present study, the role of CB1 was investigated in three different hippocampus-dependent memory tasks and in in vivo hippocampal synaptic plasticity in knockout (CB1-ko) and wildtype mice. There was no difference in short-term and long-term social and object recognition memory between CB1-ko and wildtype mice. In contrast, in background contextual fear conditioning CB1-ko mice showed enhanced freezing levels in the conditioning context and increased generalised contextual fear after a high-intensity conditioning foot shock of 1.5 mA, but not after 0.7 mA. In in vivo field potential recordings in the dentate gyrus, CB1-ko mice displayed a decreased paired-pulse facilitation of the populations spikes, suggesting an altered inhibitory synaptic drive onto hippocampal granule cells. Furthermore, CB1-ko mice displayed significantly higher levels of in vivo long-term potentiation (LTP) in the dentate gyrus. In conclusion, CB1 deficiency leads to enhanced contextual fear memory and altered synaptic plasticity in the hippocampus, supporting the key role of endocannabinoid signalling in learning and memory, in particular following highly aversive encounters.

  9. Upregulation of CD11A on Hematopoietic Stem Cells Denotes the Loss of Long-Term Reconstitution Potential

    PubMed Central

    Fathman, John W.; Fernhoff, Nathaniel B.; Seita, Jun; Chao, Connie; Scarfone, Vanessa M.; Weissman, Irving L.; Inlay, Matthew A.

    2014-01-01

    Summary Small numbers of hematopoietic stem cells (HSCs) generate large numbers of mature effector cells through the successive amplification of transiently proliferating progenitor cells. HSCs and their downstream progenitors have been extensively characterized based on their cell-surface phenotype and functional activities during transplantation assays. These cells dynamically lose and acquire specific sets of surface markers during differentiation, leading to the identification of markers that allow for more refined separation of HSCs from early hematopoietic progenitors. Here, we describe a marker, CD11A, which allows for the enhanced purification of mouse HSCs. We show through in vivo transplantations that upregulation of CD11A on HSCs denotes the loss of their long-term reconstitution potential. Surprisingly, nearly half of phenotypic HSCs (defined as Lin−KIT+SCA-1+CD150+CD34−) are CD11A+ and lack long-term self-renewal potential. We propose that CD11A+Lin−KIT+SCA-1+CD150+CD34− cells are multipotent progenitors and CD11A−Lin−KIT+SCA-1+CD150+CD34− cells are true HSCs. PMID:25418718

  10. Randomized comparison of double induction and timed-sequential induction to a "3 + 7" induction in adults with AML: long-term analysis of the Acute Leukemia French Association (ALFA) 9000 study.

    PubMed

    Castaigne, Sylvie; Chevret, Sylvie; Archimbaud, Eric; Fenaux, Pierre; Bordessoule, Dominique; Tilly, Hervé; de Revel, Thierry; Simon, Marc; Dupriez, Brigitte; Renoux, Michel; Janvier, Maud; Micléa, Jean-Michel; Thomas, Xavier; Bastard, Christian; Preudhomme, Claude; Bauters, Francis; Degos, Laurent; Dombret, Hervé

    2004-10-15

    Between 1990 and 1996, we conducted a randomized trial in adults with newly diagnosed acute myeloid leukemia (AML) in order to compare relapse-free interval (RFI) after double induction (arm B), timed-sequential induction (arm C), or control "3 + 7" induction (arm A). Patients achieving complete remission (CR) after induction +/- salvage received the same consolidation chemotherapy, which included a dosage stratification according to patient's age (younger or older than 50 years). This long-term analysis was performed in 592 patients (arm A/B/C, 197/198/197 patients). Overall CR rate was 76% without differences between the 3 arms, even if a salvage course was less frequently needed in arm B. Treatment-related mortality, either during the induction or the postremission phase, was not significantly higher in arms B and C than in arm A. Among the 449 CR patients, 250 relapsed (arm A/B/C, 90/87/73 patients) without significant differences in RFI in arms B and C versus arm A (P = .39 and .15, by the Gray test). However, when analyzing the 345 patients younger than 50, RFI was significantly improved in younger patients receiving timed-sequential induction (P = .038 by the Gray test), while not in those receiving double induction. Event-free survival and overall survival were similar in the 3 randomization arms.

  11. Long-term ultraviolet flux, other potential risk factors, and skin cancer risk: a cohort study

    PubMed Central

    Wu, Shaowei; Han, Jiali; Laden, Francine; Qureshi, Abrar A.

    2014-01-01

    Background Few prospective studies have examined the relationship between sun exposure, other potential risk factors, and risk of different skin cancers [including basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma] simultaneously. Methods We evaluated the association between a number of potential risk factors and skin cancer risk in a cohort of 108,916 US women, the Nurses’ Health Study II (1989-2009). Results During 2.05 million years of follow-up, we identified 6,955, 880, and 779 diagnoses of BCC, SCC, and melanoma, respectively. Compared to participants in the lowest quintile of cumulative ultraviolet flux in adulthood, participants in the highest quintile had multivariable-adjusted relative risks (RR) of 2.35 (Ptrend<0.0001) for BCC, 2.53 (Ptrend=0.009) for SCC, and 0.68 (Ptrend=0.38) for melanoma. In contrast, the RRs were 1.68 (95%CI: 1.55-1.82) for BCC, 1.68 (95%CI: 1.34-2.11) for SCC and 1.80 (95%CI: 1.42-2.28) for melanoma for participants with ≥5 blistering sunburns when compared to participants without sunburn between ages 15-20. We found significant interactions between family history of melanoma, number of blistering sunburns between ages 15-20 and BCC risk, and between sunburn reaction as a child/adolescent and SCC risk (all Pinteraction<0.05). Conclusion In a cohort of US women, we found that sun exposures in both early life and adulthood were predictive of BCC and SCC risks, whereas melanoma risk was predominantly associated with sun exposure in early life. Impact Our results may have potential implications for the prevention of skin cancers. PMID:24876226

  12. The E3 ligase APC/C-Cdh1 is required for associative fear memory and long-term potentiation in the amygdala of adult mice.

    PubMed

    Pick, Joseph E; Malumbres, Marcos; Klann, Eric

    2012-12-14

    The anaphase promoting complex/cyclosome (APC/C) is an E3 ligase regulated by Cdh1. Beyond its role in controlling cell cycle progression, APC/C-Cdh1 has been detected in neurons and plays a role in long-lasting synaptic plasticity and long-term memory. Herein, we further examined the role of Cdh1 in synaptic plasticity and memory by generating knockout mice where Cdh1 was conditionally eliminated from the forebrain post-developmentally. Although spatial learning and memory in the Morris water maze (MWM) was normal, the Cdh1 conditional knockout (cKO) mice displayed enhanced reversal learning in the MWM and in a water-based Y maze. In addition, we found that the Cdh1 cKO mice had impaired associative fear memory and exhibited impaired long-term potentiation (LTP) in amygdala slices. Finally, we observed increased expression of Shank1 and NR2A expression in amygdalar slices from the Cdh1 cKO mice following the induction of LTP, suggesting a possible molecular mechanism underlying the behavioral and synaptic plasticity impairments displayed in these mice. Our findings are consistent with a role for the APC/C-Cdh1 in fear memory and synaptic plasticity in the amygdala.

  13. Long term in-line sludge storage in wastewater treatment plants: the potential for phosphorus release.

    PubMed

    Johannessen, Erik; Eikum, Arild Schanke; Krogstad, Tore

    2012-12-01

    Phosphorus removal in on-site wastewater treatment plants is normally obtained by chemical precipitation. Aluminium-based chemicals are the favoured coagulants as they are not affected by redox potential. On-site wastewater treatment package plants do not have separate sludge treatment facilities, and sludge is normally collected on an annual basis. This can potentially increase the risk of phosphorus release into the water phase, subsequently reducing treatment efficiency. This study aimed to detect release of phosphorus as a result of chemical and biological processes. Variables in the study were time, aluminium dosage and pH. Wastewater sludge was monitored for 46 weeks to investigate the different mechanisms of phosphorus release and the longevity of the aluminium treatment involving varying aluminium dosages. Phosphorus compounds were analysed based on a modified Psenner sequential fractionation method. Both pH and aluminium dosage affect the longevity of the phosphorus retention of chemically precipitated wastewater sludge, where sufficient longevity is obtained with pH control and increased aluminium dosages. Chemical dosages similar to what is considered normal levels are sufficient to retain the phosphorus in the sludge for annual sludge collection intervals. Release of soluble phosphorus was attributed to microbial activity and crystallization of Al-hydroxide complexes.

  14. Brainstem auditory evoked potentials in individuals exposed to long-term low concentrations of toluene.

    PubMed

    Vrca, A; Karacić, V; Bozicević, D; Bozikov, V; Malinar, M

    1996-07-01

    Brainstem auditory evoked potentials (BAEPs) were examined in 49 workers employed in a printing press, who were occupationally exposed to low concentrations of toluene for an average of 20.3 years, and in 59 subjects in a control group. In the group of exposed workers, a significant decrease was found in all wave amplitudes examined, a significant prolongation of P1 wave latency, and an increased interval of interpeak latencies (P3-P5), indicating that the extramedullary and high medullary part of the auditory pathway are biologically most frequently affected by chronic exposure to low concentrations of toluene. The level of exposure to toluene in both groups was evaluated by defining the concentration of toluene in peripheral blood and the concentration of hippuric acid and ortho-cresol in urine.

  15. Effects of tetrahydrohyperforin in mouse hippocampal slices: neuroprotection, long-term potentiation and TRPC channels.

    PubMed

    Montecinos-Oliva, C; Schuller, A; Parodi, J; Melo, F; Inestrosa, N C

    2014-01-01

    Tetrahydrohyperforin (IDN5706) is a semi-synthetic compound derived from hyperforin (IDN5522) and is the main active principle of St. John's Wort. IDN5706 has shown numerous beneficial effects when administered to wild-type and double transgenic (APPswe/PSEN1ΔE9) mice that model Alzheimer's disease. However, its mechanism of action is currently unknown. Toward this end, we analysed field excitatory postsynaptic potentials (fEPSPs) in mouse hippocampal slices incubated with IDN5706 and in the presence of the TRPC3/6/7 activator 1-oleoyl-2-acetyl-sn-glycerol (OAG), the TRPC channel blocker SKF96365, and neurotoxic amyloid β-protein (Aβ) oligomers. To study spatial memory, Morris water maze (MWM) behavioural tests were conducted on wild-type mice treated with IDN5706 and SKF96365. In silico studies were conducted to predict a potential pharmacophore. IDN5706 and OAG had a similar stimulating effect on fEPSPs, which was inhibited by SKF96365. IDN5706 protected from reduced fEPSPs induced by Aβ oligomers. IDN5706 improved spatial memory in wild-type mice, an effect that was counteracted by co-administration of SKF96365. Our in silico studies suggest strong pharmacophore similarity of IDN5706 and other reported TRPC6 activators (IDN5522, OAG and Hyp9). We propose that the effect of IDN5706 is mediated through activation of the TRPC3/6/7 channel subfamily. The unveiling of the drug's mechanism of action is a necessary step toward the clinical use of IDN5706 in Alzheimer's disease.

  16. Long term, stable brain machine interface performance using local field potentials and multiunit spikes

    NASA Astrophysics Data System (ADS)

    Flint, Robert D.; Wright, Zachary A.; Scheid, Michael R.; Slutzky, Marc W.

    2013-10-01

    Objective. Brain machine interfaces (BMIs) have the potential to restore movement to people with paralysis. However, a clinically-viable BMI must enable consistently accurate control over time spans ranging from years to decades, which has not yet been demonstrated. Most BMIs that use single-unit spikes as inputs will experience degraded performance over time without frequent decoder re-training. Two other signals, local field potentials (LFPs) and multi-unit spikes (MSPs), may offer greater reliability over long periods and better performance stability than single-unit spikes. Here, we demonstrate that LFPs can be used in a biomimetic BMI to control a computer cursor. Approach. We implanted two rhesus macaques with intracortical microelectrodes in primary motor cortex. We recorded LFP and MSP signals from the monkeys while they performed a continuous reaching task, moving a cursor to randomly-placed targets on a computer screen. We then used the LFP and MSP signals to construct biomimetic decoders for control of the cursor. Main results. Both monkeys achieved high-performance, continuous control that remained stable or improved over nearly 12 months using an LFP decoder that was not retrained or adapted. In parallel, the monkeys used MSPs to control a BMI without retraining or adaptation and had similar or better performance, and that predominantly remained stable over more than six months. In contrast to their stable online control, both LFP and MSP signals showed substantial variability when used offline to predict hand movements. Significance. Our results suggest that the monkeys were able to stabilize the relationship between neural activity and cursor movement during online BMI control, despite variability in the relationship between neural activity and hand movements.

  17. Human Onchocerciasis: Modelling the Potential Long-term Consequences of a Vaccination Programme

    PubMed Central

    Turner, Hugo C.; Walker, Martin; Lustigman, Sara; Taylor, David W.; Basáñez, María-Gloria

    2015-01-01

    Background Currently, the predominant onchocerciasis control strategy in Africa is annual mass drug administration (MDA) with ivermectin. However, there is a consensus among the global health community, supported by mathematical modelling, that onchocerciasis in Africa will not be eliminated within proposed time frameworks in all endemic foci with only annual MDA, and novel and alternative strategies are urgently needed. Furthermore, use of MDA with ivermectin is already compromised in large areas of central Africa co-endemic with Loa loa, and there are areas where suboptimal or atypical responses to ivermectin have been documented. An onchocerciasis vaccine would be highly advantageous in these areas. Methodology/Principal Findings We used a previously developed onchocerciasis transmission model (EPIONCHO) to investigate the impact of vaccination in areas where loiasis and onchocerciasis are co-endemic and ivermectin is contraindicated. We also explore the potential influence of a vaccination programme on infection resurgence in areas where local elimination has been successfully achieved. Based on the age range included in the Expanded Programme on Immunization (EPI), the vaccine was assumed to target 1 to 5 year olds. Our modelling results indicate that the deployment of an onchocerciasis vaccine would have a beneficial impact in onchocerciasis–loiasis co-endemic areas, markedly reducing microfilarial load in the young (under 20 yr) age groups. Conclusions/Significance An onchocerciasis prophylactic vaccine would reduce the onchocerciasis disease burden in populations where ivermectin cannot be administered safely. Moreover, a vaccine could substantially decrease the chance of re-emergence of Onchocerca volvulus infection in areas where it is deemed that MDA with ivermectin can be stopped. Therefore, a vaccine would protect the substantial investments made by present and past onchocerciasis control programmes, decreasing the chance of disease recrudescence and

  18. Evidence that heterosynaptic depolarization underlies associativity of long-term potentiation in rat hippocampus.

    PubMed

    Clark, K A; Collingridge, G L

    1996-01-15

    1. Whole-cell patch-clamp recording has been used to study the effect of heterosynaptic depolarization on pure N-methyl-D-aspartate (NMDA) receptor-mediated synaptic transmission in the CA1 region of rat hippocampal slices. 2. In neurones voltage clamped at -60 mV, paired-pulse stimulation of one set of Schaffer collateral-commissural fibres resulted in homosynaptic paired-pulse facilitation of the NMDA receptor-mediated excitatory postsynaptic current (EPSCN). In contrast, stimulation of one set of fibres prior to stimulation of a second set of fibres (i.e. heterosynaptic paired-pulse stimulation) did not result in any heterosynaptic interactions. 3. However, under current-clamp conditions, heterosynaptic paired-pulse stimulation resulted in heterosynaptic 'paired-pulse facilitation' of the NMDA receptor-mediated excitatory postsynaptic potential (EPSPN). 4. In neurones held at -50 or -40 mV, perfusion of nominally Mg(2+)-free medium converted the response to heterosynaptic paired-pulse stimulation from 'heterosynaptic facilitation' to 'heterosynaptic depression' of EPSPN. 5. When neurones were held at potentials of between -30 and +40 mV then heterosynaptic paired-pulse stimulation, in normal Mg(2+)-containing medium, resulted in 'paired-pulse depression' of EPSPN. Under voltage-clamp conditions (tested at +40 mV) no heterosynaptic interactions were seen. 6. The time course of 'heterosynaptic facilitation' at -60 mV and of 'heterosynaptic depression' at +40 mV of EPSPN was similar to the time course of EPSCN. 7. We conclude, firstly, that the voltage clamp is able to prevent any voltage breakthrough associated with the synaptic activation of NMDA receptors from influencing neighbouring synapses. Secondly, when the neurone is not voltage clamped these same synapses are strongly influenced by the spreading depolarization generated by the synaptic activation of their neighbours. The time course and direction of this influence are compatible with the hypothesis that

  19. Long-Term Warming Alters Carbohydrate Degradation Potential in Temperate Forest Soils.

    PubMed

    Pold, Grace; Billings, Andrew F; Blanchard, Jeff L; Burkhardt, Daniel B; Frey, Serita D; Melillo, Jerry M; Schnabel, Julia; van Diepen, Linda T A; DeAngelis, Kristen M

    2016-11-15

    As Earth's climate warms, soil carbon pools and the microbial communities that process them may change, altering the way in which carbon is recycled in soil. In this study, we used a combination of metagenomics and bacterial cultivation to evaluate the hypothesis that experimentally raising soil temperatures by 5°C for 5, 8, or 20 years increased the potential for temperate forest soil microbial communities to degrade carbohydrates. Warming decreased the proportion of carbohydrate-degrading genes in the organic horizon derived from eukaryotes and increased the fraction of genes in the mineral soil associated with Actinobacteria in all studies. Genes associated with carbohydrate degradation increased in the organic horizon after 5 years of warming but had decreased in the organic horizon after warming the soil continuously for 20 years. However, a greater proportion of the 295 bacteria from 6 phyla (10 classes, 14 orders, and 34 families) isolated from heated plots in the 20-year experiment were able to depolymerize cellulose and xylan than bacterial isolates from control soils. Together, these findings indicate that the enrichment of bacteria capable of degrading carbohydrates could be important for accelerated carbon cycling in a warmer world.

  20. Robustness of retrieval properties against imbalance between long-term potentiation and depression of spike-timing-dependent plasticity

    NASA Astrophysics Data System (ADS)

    Matsumoto, Narihisa; Okada, Masato

    2003-12-01

    Spike-timing-dependent plasticity (STDP) has recently been shown in some physiological studies. STDP depends on the precise temporal relationship of presynaptic and postsynaptic spikes. Many authors have indicated that a precise balance between long-term potentiation (LTP) and long-term depression (LTD) of STDP is significant for a stable learning. However, a situation in which the balance is maintained precisely is inconceivable in the brain. Using a method of the statistical neurodynamics, we show robust retrieval properties of spatiotemporal patterns in an associative memory model against the imbalance between LTP and LTD. When the fluctuation of LTD is assumed to obey a Gaussian distribution with mean 0 and variance δ2, the storage capacity takes a finite value even at large δ. This means that the balance between LTP and LTD of STDP need not be maintained precisely, but must be maintained on average. Furthermore, we found that the basin of attraction becomes smaller as δ increases while an initial critical overlap remains unchanged.

  1. Forebrain NR2B overexpression enhancing fear acquisition and long-term potentiation in the lateral amygdala.

    PubMed

    Duan, Yanhong; Zhou, Siqi; Ma, Jing; Yin, Pengcheng; Cao, Xiaohua

    2015-09-01

    N-methyl-d-aspartic acid (NMDA) receptor-dependent long-term potentiation (LTP) at the thalamus-lateral amygdala (T-LA) synapses is the basis for acquisition of auditory fear memory. However, the role of the NMDA receptor NR2B subunit in synaptic plasticity at T-LA synapses remains speculative. In the present study, using transgenic mice with forebrain-specific overexpression of the NR2B subunit, we have observed that forebrain NR2B overexpression results in enhanced LTP but does not alter long-term depression (LTD) at the T-LA synapses in transgenic mice. To elucidate the cellular mechanisms underlying enhanced LTP at T-LA synapses in these transgenic mice, AMPA and NMDA receptor-mediated postsynaptic currents have been measured. The data show a marked increasing in the amplitude and decay time of NMDA receptor-mediated currents in these transgenic mice. Consistent with enhanced LTP at T-LA synapses, NR2B-transgenic mice exhibit better performance in the acquisition of auditory fear memory than wild-type littermates. Our results demonstrate that up-regulation of NR2B expression facilitates acquisition of auditory cued fear memory and enhances LTP at T-LA synapses.

  2. Nicotine blocks stress-induced impairment of spatial memory and long-term potentiation of the hippocampal CA1 region.

    PubMed

    Aleisa, Abdulaziz M; Alzoubi, Karem H; Gerges, Nashaat Z; Alkadhi, Karim A

    2006-08-01

    The effect of chronic nicotine treatment on chronic psychosocial stress-induced impairment of short-term memory and long-term potentiation (LTP) was determined. An "intruder" stress model was used to induce psychosocial stress for 4-6 wk, during which rats were injected with saline or nicotine (1 mg/kg s.c.) twice a day. The radial arm water maze memory task was used to test hippocampus-dependent spatial memory. Chronic psychosocial stress impaired short-term memory without affecting the learning phase or long-term memory. Concurrent chronic nicotine treatment prevented stress-induced short-term memory impairment. In normal rats chronic nicotine treatment had no effect on learning and memory. Extracellular recordings from the CA1 region of anaesthetized rats showed severe reduction of LTP magnitude in stressed rats, which was normalized in nicotine-treated stressed rats. Nicotine had no effect on LTP in control animals. These results showed that chronic nicotine treatment improved hippocampus-dependent spatial memory and LTP only when impaired by stress.

  3. Differential modulation of short-term synaptic dynamics by long-term potentiation at mouse hippocampal mossy fibre synapses.

    PubMed

    Gundlfinger, Anja; Leibold, Christian; Gebert, Katja; Moisel, Marion; Schmitz, Dietmar; Kempter, Richard

    2007-12-15

    Synapses continuously experience short- and long-lasting activity-dependent changes in synaptic strength. Long-term plasticity refers to persistent alterations in synaptic efficacy, whereas short-term plasticity (STP) reflects the instantaneous and reversible modulation of synaptic strength in response to varying presynaptic stimuli. The hippocampal mossy fibre synapse onto CA3 pyramidal cells is known to exhibit both a presynaptic, NMDA receptor-independent form of long-term potentiation (LTP) and a pronounced form of STP. A detailed description of their exact interdependence is, however, lacking. Here, using electrophysiological and computational techniques, we have developed a descriptive model of transmission dynamics to quantify plasticity at the mossy fibre synapse. STP at this synapse is best described by two facilitatory processes acting on time-scales of a few hundred milliseconds and about 10 s. We find that these distinct types of facilitation are differentially influenced by LTP such that the impact of the fast process is weakened as compared to that of the slow process. This attenuation is reflected by a selective decrease of not only the amplitude but also the time constant of the fast facilitation. We henceforth argue that LTP, involving a modulation of parameters determining both amplitude and time course of STP, serves as a mechanism to adapt the mossy fibre synapse to its temporal input.

  4. The Greenville Fault: preliminary estimates of its long-term creep rate and seismic potential

    USGS Publications Warehouse

    Lienkaemper, James J.; Barry, Robert G.; Smith, Forrest E.; Mello, Joseph D.; McFarland, Forrest S.

    2013-01-01

    Once assumed locked, we show that the northern third of the Greenville fault (GF) creeps at 2 mm/yr, based on 47 yr of trilateration net data. This northern GF creep rate equals its 11-ka slip rate, suggesting a low strain accumulation rate. In 1980, the GF, easternmost strand of the San Andreas fault system east of San Francisco Bay, produced a Mw5.8 earthquake with a 6-km surface rupture and dextral slip growing to ≥2 cm on cracks over a few weeks. Trilateration shows a 10-cm post-1980 transient slip ending in 1984. Analysis of 2000-2012 crustal velocities on continuous global positioning system stations, allows creep rates of ~2 mm/yr on the northern GF, 0-1 mm/yr on the central GF, and ~0 mm/yr on its southern third. Modeled depth ranges of creep along the GF allow 5-25% aseismic release. Greater locking in the southern two thirds of the GF is consistent with paleoseismic evidence there for large late Holocene ruptures. Because the GF lacks large (>1 km) discontinuities likely to arrest higher (~1 m) slip ruptures, we expect full-length (54-km) ruptures to occur that include the northern creeping zone. We estimate sufficient strain accumulation on the entire GF to produce Mw6.9 earthquakes with a mean recurrence of ~575 yr. While the creeping 16-km northern part has the potential to produce a Mw6.2 event in 240 yr, it may rupture in both moderate (1980) and large events. These two-dimensional-model estimates of creep rate along the southern GF need verification with small aperture surveys.

  5. Purification and long-term expansion of multipotent endothelial-like cells with potential cardiovascular regeneration.

    PubMed

    Marchal, Juan A; Picón, Manuel; Perán, Macarena; Bueno, Clara; Jiménez-Navarro, Manuel; Carrillo, Esmeralda; Boulaiz, Houria; Rodríguez, Noela; Álvarez, Pablo; Menendez, Pablo; de Teresa, Eduardo; Aránega, Antonia

    2012-03-01

    Endothelial progenitor cells (EPC) represent a relatively rare cell population, and expansion of sufficient cell numbers remains a challenge. Nevertheless, human adipose-derived stem cells (hASC) can be easily isolated and possess the ability to differentiate into endothelial cells. Here, we propose the isolation and characterization of multipotent endothelial-like cells (ME-LC) with the capacity to maintain their vascular progenitor properties for long periods. hASC were isolated from lipoaspirates and cultured through distinct consecutive culture stages for 2 months to enrich ME-LC: first in Dulbecco's modified Eagle's medium-fetal bovine serum (stage I), followed by a stage of culture in absent of fetal bovine serum (stage II), a culture in SFO3 medium (stage III), and, finally, the culture of ME-LC into collagen IV-coated flasks in endothelial growth medium (EGM-2) (stage IV). ME-LC display increased expression levels of endothelial and hematopoietic lineage markers (CD45, KDR, and CXCR4) and EPC markers (CD34 and CD133), whereas the expression of CD31 was barely detectable. Reverse transcription (RT)-polymerase chain reaction assays showed expression of genes involved in early stages of EPC differentiation and decreased expression of genes associated to differentiated EPC (TIE-2, DLL4, and FLT-1). ME-LC formed capillary-like structures when grown on Matrigel, secreted increased levels of stromal cell-derived factor-1 (SDF-1), and showed the ability to migrate attracted by SDF-1, vascular endothelial growth factor, and hematopoietic growth factor cytokines. Importantly, ME-LC retained the capacity to differentiate into cardiomyocyte-like cells. We present a simplified and efficient method to generate large numbers of autologous ME-LC from lipoaspirates-derived hASC, opening up potential cell-based therapies for cardiovascular regenerative medicine.

  6. Natural immune boosting in pertussis dynamics and the potential for long-term vaccine failure.

    PubMed

    Lavine, Jennie S; King, Aaron A; Bjørnstad, Ottar N

    2011-04-26

    Incidence of whooping cough, unlike many other childhood diseases for which there is an efficacious vaccine, has been increasing over the past twenty years despite high levels of vaccine coverage. Its reemergence has been particularly noticeable among teenagers and adults. Many hypotheses have been put forward to explain these two patterns, but parsimonious reconciliation of clinical data on the limited duration of immunity with both pre- and postvaccine era age-specific incidence remains a challenge. We consider the immunologically relevant, yet epidemiologically largely neglected, possibility that a primed immune system can respond to a lower dose of antigen than a naive one. We hypothesize that during the prevaccine era teenagers' and adults' primed immunity was frequently boosted by reexposure, so maintaining herd immunity in the face of potentially eroding individual immunity. In contrast, low pathogen circulation in the current era, except during epidemic outbreaks, allows immunity to be lost before reexposure occurs. We develop and analyze an age-structured model that encapsulates this hypothesis. We find that immune boosting must be more easily triggered than primary infection to account for age-incidence data. We make age-specific and dynamical predictions through bifurcation analysis and simulation. The boosting model proposed here parsimoniously captures four key features of pertussis data from highly vaccinated countries: (i) the shift in age-specific incidence, (ii) reemergence with high vaccine coverage, (iii) the possibility for cyclic dynamics in the pre- and postvaccine eras, and (iv) the apparent shift from susceptible-infectious-recovered (SIR)-like to susceptible-infectious-recovered-susceptible (SIRS)-like phenomenology of infection and immunity to Bordetella pertussis.

  7. Long-Term Warming Alters Carbohydrate Degradation Potential in Temperate Forest Soils

    PubMed Central

    Billings, Andrew F.; Blanchard, Jeff L.; Burkhardt, Daniel B.; Frey, Serita D.; Melillo, Jerry M.; Schnabel, Julia; van Diepen, Linda T. A.

    2016-01-01

    ABSTRACT As Earth's climate warms, soil carbon pools and the microbial communities that process them may change, altering the way in which carbon is recycled in soil. In this study, we used a combination of metagenomics and bacterial cultivation to evaluate the hypothesis that experimentally raising soil temperatures by 5°C for 5, 8, or 20 years increased the potential for temperate forest soil microbial communities to degrade carbohydrates. Warming decreased the proportion of carbohydrate-degrading genes in the organic horizon derived from eukaryotes and increased the fraction of genes in the mineral soil associated with Actinobacteria in all studies. Genes associated with carbohydrate degradation increased in the organic horizon after 5 years of warming but had decreased in the organic horizon after warming the soil continuously for 20 years. However, a greater proportion of the 295 bacteria from 6 phyla (10 classes, 14 orders, and 34 families) isolated from heated plots in the 20-year experiment were able to depolymerize cellulose and xylan than bacterial isolates from control soils. Together, these findings indicate that the enrichment of bacteria capable of degrading carbohydrates could be important for accelerated carbon cycling in a warmer world. IMPORTANCE The massive carbon stocks currently held in soils have been built up over millennia, and while numerous lines of evidence indicate that climate change will accelerate the processing of this carbon, it is unclear whether the genetic repertoire of the microbes responsible for this elevated activity will also change. In this study, we showed that bacteria isolated from plots subject to 20 years of 5°C of warming were more likely to depolymerize the plant polymers xylan and cellulose, but that carbohydrate degradation capacity is not uniformly enriched by warming treatment in the metagenomes of soil microbial communities. This study illustrates the utility of combining culture-dependent and culture

  8. Airborne Electromagnetic Surveys for Baseline Permafrost Mapping and Potential Long-Term Monitoring

    NASA Astrophysics Data System (ADS)

    Smith, B. D.; Walvoord, M. A.; Cannia, J. C.; Voss, C. I.

    2010-12-01

    Concerns over the impacts of climate change have recently energized research on permafrost and the potential impacts that thawing permafrost may have on groundwater flow, infrastructure, ecosystems, and contaminant transport. There is typically little known at watershed or regional scales about the three-dimensional distribution of permafrost, including its thickness and the distribution of taliks (unfrozen zones), and other permafrost features thereby impeding the assessment of consequences of permafrost degradation. Airborne remote sensing methods for mapping permafrost are attractive, particularly in arctic and subarctic studies where ground access is difficult and ecosystems are fragile. As part of its Climate Effect Network (CEN) research and observation effort in the Yukon River Basin, the U.S. Geological Survey (USGS) has initiated an effort to map permafrost using airborne geophysics to complement hydrologic and biogeochemical studies in the study area. Interpretation of airborne geophysical data will be integrated with other remotely sensed data to supply critical hydrogeologic information needed for refining groundwater flow models in the Yukon Flats Basin. Airborne surveys also provide baseline data for estimating 3D permafrost distribution that can be compared to future permafrost surveys to estimate a volumetric change over time. In June 2010, the USGS conducted a helicopter frequency domain electromagnetic (HFEM) survey in the area of Fort Yukon, Alaska to map permafrost distribution. Flight line data processing has been completed that includes data leveling and a simple transformation to resistivity-depth along the flight lines. Preliminary resistivity-depth images from the survey can be qualitatively compared with known permafrost features and used to establish new permafrost features. Electrical properties of earth materials are impacted by temperature and the presence of ice causing them to become substantially more resistive when frozen. The area

  9. Potential long-term effects of previous schistosome infection may reduce the atherogenic index of plasma in Chinese men.

    PubMed

    Shen, Shi-Wei; Lu, Yun; Li, Feng; Shen, Zhen-Hai; Xu, Ming; Yao, Wei-Feng; Feng, Yin-Bo; Yun, Jing-Ting; Wang, Ya-Ping; Ling, Wang; Qi, Hua-Jin; Tong, Da-Xin

    2015-04-01

    The major purpose of this study was to assess the association between the potential long-term effects of previous schistosome infection and atherogenic dyslipidemia. Among 1597 men aged ⩾45 years who received health examinations and lived in previous schistosomiasis-endemic regions of China, 465 patients with previous schistosome infection were selected as study subjects, and 1132 subjects formed the control group. The risk factors for cardiovascular disease were measured and compared between the previous schistosome infection and control groups. The Atherogenic Index of Plasma, triglycerides, waist circumference and body mass index were significantly lower in the previous schistosome infection group than in the control group (all P values <0.001), whereas high-density lipoprotein-cholesterol was significantly higher in the previous schistosome infection group (P<0.001). In the Atherogenic Index of Plasma quartiles (Q1-Q4), the percentages of subjects with previous schistosome infection were 55.89% (Q1), 25.44% (Q2), 16.33% (Q3), and 18.8% (Q4), respectively (χ(2)=139.86, P<0.001). A logistic regression analysis based on previous schistosome infection as the independent variable and Atherogenic Index of Plasma as the dependent variable revealed that previous schistosome infection was significantly negatively correlated with Atherogenic Index of Plasma (odds ratio=0.583, 95% confidence interval: 0.440-0.772, P<0.001) after adjustment for body mass index, waist circumference, diastolic blood pressure and uric acid, suggesting that previous schistosome infection is an independent factor associated with Atherogenic Index of Plasma. The potential long-term effects of previous schistosome infection may reduce the Atherogenic Index of Plasma in Chinese men. However, further studies are required to investigate the protective human immune response against schistosome infections. The development of a schistosomiasis vaccine may effectively prevent the development and

  10. Long-term no-till and stover retention each decrease the global warming potential of irrigated continuous corn.

    PubMed

    Jin, Virginia L; Schmer, Marty R; Stewart, Catherine E; Sindelar, Aaron J; Varvel, Gary E; Wienhold, Brian J

    2017-01-30

    Over the last 50 years, the most increase in cultivated land area globally has been due to a doubling of irrigated land. Long-term agronomic management impacts on soil organic carbon (SOC) stocks, soil greenhouse gas (GHG) emissions, and global warming potential (GWP) in irrigated systems, however, remain relatively unknown. Here, residue and tillage management effects were quantified by measuring soil nitrous oxide (N2 O) and methane (CH4 ) fluxes and SOC changes (ΔSOC) at a long-term, irrigated continuous corn (Zea mays L.) system in eastern Nebraska, United States. Management treatments began in 2002, and measured treatments included no or high stover removal (0 or 6.8 Mg DM ha(-1)  yr(-1) , respectively) under no-till (NT) or conventional disk tillage (CT) with full irrigation (n = 4). Soil N2 O and CH4 fluxes were measured for five crop-years (2011-2015), and ΔSOC was determined on an equivalent mass basis to ~30 cm soil depth. Both area- and yield-scaled soil N2 O emissions were greater with stover retention compared to removal and for CT compared to NT, with no interaction between stover and tillage practices. Methane comprised <1% of total emissions, with NT being CH4 neutral and CT a CH4 source. Surface SOC decreased with stover removal and with CT after 14 years of management. When ΔSOC, soil GHG emissions, and agronomic energy usage were used to calculate system GWP, all management systems were net GHG sources. Conservation practices (NT, stover retention) each decreased system GWP compared to conventional practices (CT, stover removal), but pairing conservation practices conferred no additional mitigation benefit. Although cropping system, management equipment/timing/history, soil type, location, weather, and the depth to which ΔSOC is measured affect the GWP outcomes of irrigated systems at large, this long-term irrigated study provides valuable empirical evidence of how management decisions can impact soil GHG emissions and surface SOC

  11. A Primary Cortical Input to Hippocampus Expresses a Pathway-Specific and Endocannabinoid-Dependent Form of Long-Term Potentiation

    PubMed Central

    Wang, Weisheng; Jia, Yousheng; Pham, Danielle T.; Karsten, Carley A.; Merrill, Collin B.; Gall, Christine M.; Piomelli, Daniele

    2016-01-01

    Abstract The endocannabinoid 2-arachidonoyl-sn-glycerol (2-AG), a key modulator of synaptic transmission in mammalian brain, is produced in dendritic spines and then crosses the synaptic junction to depress neurotransmitter release. Here we report that 2-AG-dependent retrograde signaling also mediates an enduring enhancement of glutamate release, as assessed with independent tests, in the lateral perforant path (LPP), one of two cortical inputs to the granule cells of the dentate gyrus. Induction of this form of long-term potentiation (LTP) involved two types of glutamate receptors, changes in postsynaptic calcium, and the postsynaptic enzyme that synthesizes 2-AG. Stochastic optical reconstruction microscopy confirmed that CB1 cannabinoid receptors are localized presynaptically to LPP terminals, while the inhibition or knockout of the receptors eliminated LPP-LTP. Suppressing the enzyme that degrades 2-AG dramatically enhanced LPP potentiation, while overexpressing it produced the opposite effect. Priming with a CB1 agonist markedly reduced the threshold for LTP. Latrunculin A, which prevents actin polymerization, blocked LPP-LTP when applied extracellularly but had no effect when infused postsynaptically into granule cells, indicating that critical actin remodeling resides in the presynaptic compartment. Importantly, there was no evidence for the LPP form of potentiation in the Schaffer-commissural innervation of field CA1 or in the medial perforant path. Peripheral injections of compounds that block or enhance LPP-LTP had corresponding effects on the formation of long-term memory for cues conveyed to the dentate gyrus by the LPP. Together, these results indicate that the encoding of information carried by a principal hippocampal afferent involves an unusual, regionally differentiated form of plasticity. PMID:27517090

  12. Metabolic Profile as a Potential Modifier of Long-Term Radiation Effects on Peripheral Lymphocyte Subsets in Atomic Bomb Survivors.

    PubMed

    Yoshida, Kengo; Nakashima, Eiji; Kyoizumi, Seishi; Hakoda, Masayuki; Hayashi, Tomonori; Hida, Ayumi; Ohishi, Waka; Kusunoki, Yoichiro

    2016-09-01

    Immune system impairments reflected by the composition and function of circulating lymphocytes are still observed in atomic bomb survivors, and metabolic abnormalities including altered blood triglyceride and cholesterol levels have also been detected in such survivors. Based on closely related features of immune and metabolic profiles of individuals, we investigated the hypothesis that long-term effects of radiation exposure on lymphocyte subsets might be modified by metabolic profiles in 3,113 atomic bomb survivors who participated in health examinations at the Radiation Effect Research Foundation, Hiroshima and Nagasaki, in 2000-2002. The lymphocyte subsets analyzed involved T-, B- and NK-cell subsets, and their percentages in the lymphocyte fraction were assessed using flow cytometry. Health examinations included metabolic indicators, body mass index, serum levels of total cholesterol, high-density lipoprotein cholesterol, C-reactive protein and hemoglobin A1c, as well as diabetes and fatty liver diagnoses. Standard regression analyses indicated that several metabolic indicators of obesity/related disease, particularly high-density lipoprotein cholesterol levels, were positively associated with type-1 helper T- and B-cell percentages but were inversely associated with naïve CD4 T and NK cells. A regression analysis adjusted for high-density lipoprotein cholesterol revealed a radiation dose relationship with increasing NK-cell percentage. Additionally, an interaction effect was suggested between radiation dose and C-reactive protein on B-cell percentage with a negative coefficient of the interaction term. Collectively, these findings suggest that radiation exposure and subsequent metabolic profile changes, potentially in relationship to obesity-related inflammation, lead to such long-term alterations in lymphocyte subset composition. Because this study is based on cross-sectional and exploratory analyses, the implications regarding radiation exposure, metabolic

  13. Long-term potential nonlinear predictability of El Niño-La Niña events

    NASA Astrophysics Data System (ADS)

    Astudillo, H. F.; Abarca-del-Río, R.; Borotto, F. A.

    2016-08-01

    We show that the monthly recorded history (1866-2014) of the Southern Oscillation Index (SOI), a descriptor of the El Niño Southern Oscillation (ENSO) phenomenon, can be correctly described as a dynamic system supporting a potential nonlinear predictability well beyond the spring barrier. Long-term predictability is strongly connected to a detailed knowledge about the topology of the attractor obtained by embedding the SOI index in a wavelet base state space. By utilizing the state orbits on the attractor, we show that the information contained in the SOI is sufficient to provide nonlinear attractor information, allowing the detection of predictability for longer than a year: 2, 3, and 4 years in advance throughout the record with an acceptable error. This is possible due to the fact that the lower-frequency variability of the SOI presents long-term positive autocorrelation. Thus, by using complementary methods, we confirm that the reconstructed attractor of the low-frequency part (lower than 1/year) of SOI time series cannot be attributed to stochastic influences. Furthermore, we establish its multifractality. As an example of the capabilities of the methodology, we investigate a few specific El Niño (1972-1973, 1982-1983, 1997-1998) and La Niña (1973-1973, 1988-1989 and 2010-2011) events. Our results indicate that each of these present several equivalent temporal structures over other eras of these 149 years (1866-2014). Accordingly, none of these cases, including extreme events, presents temporal singularity. We conclude that the methodology's simplicity of implementation and ease of use makes it suitable for studying nonlinear predictability in any area where observations are similar to those describing the ENSO phenomenon.

  14. Drivers, trends, and potential impacts of long-term coastal reclamation in China from 1985 to 2010

    NASA Astrophysics Data System (ADS)

    Tian, Bo; Wu, Wenting; Yang, Zhaoqing; Zhou, Yunxuan

    2016-03-01

    The reclamation of coastal land for agricultural, industrial, and urban land use-a common worldwide practice-has occurred extensively in the coastal region of China. In recent decades, all coastal provinces and metropolises in China have experienced severe coastal reclamation related to land scarcity caused by rapid economic growth and urbanization. However, the value of coastal wetlands and ecosystems has not been well understood and appreciated until recent development of advantageous methods of restoring reclaimed land to coastal wetlands in many developed countries. The overall objective of this study is to provide detailed spatial and temporal distributions of coastal reclamation; analyze drivers such as coastal economy, population growth, and urbanization; and understand the relationships among the drivers and land reclamation. We used long-term Landsat image time series from 1985 to 2010 in 5-year intervals, in combination with remotely sensed image interpretation and spatial analysis, to map the reclamation status and changes across the coastal region of China. The Landsat images time-series analysis was also conducted to evaluate the effects of the economy, population, and urbanization drivers on coastal reclamation. The analysis results indicated that 754,697 ha of coastal wetlands have been reclaimed across all coastal provinces and metropolises from 1985 to 2010, and the trend increased sharply after 2005. High-intensity coastal reclamation was mainly driven by the booming economy, especially after 2000, associated with urbanization and industrial development in China's coastal region; this was closely correlated with the gross domestic product (GDP) per capita. The continuous large-scale coastal reclamation of its coastal region now means China is facing a great challenge, including the enormous loss of vegetated coastal wetlands, negative environmental effects, and potential disaster risks related to coastal flooding under future change climate

  15. Acid rock drainage passive remediation: Potential use of alkaline clay, optimal mixing ratio and long-term impacts.

    PubMed

    Plaza, Fernando; Wen, Yipei; Perone, Hanna; Xu, Yi; Liang, Xu

    2017-01-15

    Acid rock drainage (ARD) is one of the most adverse environmental problems of the mining industry. Surface and ground water affected by this pollution are characterized by their acidity and the high content of sulfates and metals/metalloids. In this study, alkaline clay (AC), an industrial waste with a high alkalinity, which is utilized in the alumina refining process, was used as the remediation material to inhibit pyrite oxidation in waste coal piles. Through a series of laboratory experiments (static and kinetic), complemented with field measurements and geochemical modeling, three important issues associated with this passive and sustainable ARD remediation method were investigated: 1) the potential use of alkaline clay as an ARD remediation material, 2) the adequate alkaline clay/coal refuse mixing ratio (AC/CR) to ensure pH values close to neutral conditions, and, 3) the implications for long-term performance, in terms of the trends of the main parameters involved in this process such as pH, concentrations of sulfate, iron and other dissolved contaminants. Both field measurements and the samples used for the experiments came from a local waste coal site. Through the analysis of the field measurements and the outcome of the laboratory experiments, AC proved to be an effective remediation material for ARD. Compared to those found in mine tailings, the concentrations of contaminants such as iron, manganese or sulfate were significantly reduced with this remediation approach. Moreover, results suggest a reliable long-term stability of the remediation (i.e. neutral pH conditions are maintained), thus enhancing the generation of iron precipitates that could produce pyrite grain coating. These processes also made the amended layer less porous, thus increased water retention and hindered oxygen diffusion.

  16. Acid Mine Drainage Passive Remediation: Potential Use of Alkaline Clay, Optimal Mixing Ratio and Long Term Impacts

    NASA Astrophysics Data System (ADS)

    Plaza, F.; Liang, X.; Wen, Y.; Perone, H.

    2015-12-01

    Acid mine drainage (AMD) is one of the most adverse environmental problems of the mine industry. Surface water and ground water affected by this pollution are characterized by their acidity and the high content of sulfates and heavy metals. In this study, alkaline clay, an industrial waste with a high pH, which is utilized in the alumina refining process, was used as the remediation material to inhibit pyrite oxidation. Through a series of batch and column experiments, complemented with field measurements and geochemical modeling, three important issues associated with this passive and auto sustainable acid mine drainage remediation method were investigated: 1) the potential use of alkaline clay as an AMD remediation material, 2) the adequate alkaline clay/coal refuse mixing ratio (AC/CR) to ensure pH values near to neutral conditions, and, 3) the prediction of long term impacts, in terms of the trends of the main parameters involved in this process such as pH, concentrations of sulfate, iron and other dissolved contaminants. Both field measurements and the samples used for the experiments came from a coal waste site located in Mather, Pennsylvania. Alkaline clay proved to be an effective remediation material for AMD. It was found that 10% AC/CR is an adequate mixing ratio (i.e. the upper limit), which has been also indicated by field measurements. The concentrations of some contaminants such as iron, manganese or sulfate are significantly reduced with the remediation approach, compared to those representative concentrations found in mine tailings. Moreover, results suggest a very reliable long-term stability of the remediation (i.e. neutral pH conditions are maintained), thus enhancing the generation of iron precipitates that could produce pyrite grain coating and hardpan (i.e. cemented layer) on the surface. These processes also made the amended layer less porous, thus increasing water retention and hindering oxygen diffusion.

  17. EPSP-spike potentiation during primed burst-induced long-term potentiation in the CA1 region of rat hippocampal slices.

    PubMed

    Pugliese, A M; Ballerini, L; Passani, M B; Corradetti, R

    1994-10-01

    Long-term potentiation induced by high-frequency stimulation in the CA1 region of the hippocampus exhibits EPSP-spike potentiation. This consists of an increase in population spike amplitude exceeding that predicted by EPSP potentiation alone. This phenomenon is apparently due to an increase in pyramidal cell excitability. Patterns of afferent stimuli which activate pyramidal cells to reproduce the theta rhythm observed in the hippocampus under physiological conditions, have been shown to induce LTP-like enhancement of synaptic responses in vitro. The aim of this study was to investigate the presence of EPSP-spike potentiation and/or changes in pyramidal cell excitability during the long-term potentiation induced in the CA1 region of rat hippocampal slices by theta-like patterns of stimuli: the primed burst and the patterned stimulation. Using extracellular recording, a significant leftward shift in the EPSP-spike relationship was found 30 min after primed burst or patterned stimulation. The magnitude of EPSP-spike potentiation induced by patterned stimulation was similar to that produced by high-frequency stimulation. Both were significantly greater than that induced by a primed burst, indicating that only a subset of pyramidal cells were potentiated by this kind of afferent activation. Modifications in synaptic efficacy and cell excitability brought about by a primed burst were investigated in 25 intracellularly recorded pyramidal cells. Consistent with extracellular results, it was found that only 11 out of 25 neurons receiving a primed burst were potentiated. In these cells the increase in probability of firing action potentials elicited by synaptic activation with test shocks was accompanied by enhanced cell excitability, but not by an increase in EPSP slope. High-frequency stimulation delivered 40 min after a primed burst invariably increased the EPSP slope, the probability of firing upon synaptic stimulation, and the excitability of cells. The presence of

  18. Corticosterone time-dependently modulates β-adrenergic effects on long-term potentiation in the hippocampal dentate gyrus

    PubMed Central

    Pu, Zhenwei; Krugers, Harm J.; Joëls, Marian

    2007-01-01

    Previous experiments in the hippocampal CA1 area have shown that corticosterone can facilitate long-term potentiation (LTP) in a rapid non-genomic fashion, while the same hormone suppresses LTP that is induced several hours after hormone application. Here, we elaborated on this finding by examining whether corticosterone exerts opposite effects on LTP depending on the timing of hormone application in the dentate gyrus as well. Moreover, we tested rapid and delayed actions by corticosterone on β-adrenergic-dependent changes in LTP. Unlike the CA1 region, our in vitro field potential recordings show that rapid effects of corticosterone do not influence LTP induced by mild tetanization in the hippocampal dentate gyrus, unless GABAA receptors are blocked. In contrast, the β-adrenergic agonist isoproterenol does initiate a slow-onset, limited amount of potentiation. When corticosterone was applied concurrently with isoproterenol, a further enhancement of synaptic strength was identified, especially during the early stage of potentiation. Yet, treatment with corticosterone several hours in advance of isoproterenol fully prevented any effect of isoproterenol on LTP. This emphasizes that corticosterone can regulate β-adrenergic modulation of synaptic plasticity in opposite directions, depending on the timing of hormone application. PMID:17522027

  19. The effect of positive mood induction on reducing reinstatement fear: Relevance for long term outcomes of exposure therapy

    PubMed Central

    Zbozinek, Tomislav D.; Holmes, Emily A.; Craske, Michelle G.

    2015-01-01

    While exposure therapy is effective in treating anxiety, fear can return after exposure. Return of fear can be understood through mechanisms of extinction learning. One form of return of fear is reinstatement, or, the fear that results from an unsignaled unconditional stimulus (US) presentation after extinction. Though the conditional response (CR; e.g., fear) typically reduces during extinction, the excitatory conditional stimulus (CS+) valence remains negative. The more negative the CS+ valence after the end of extinction, the greater the fear at reinstatement. The current study evaluated the degree to which positive mood induction (positive imagery training; PIT) compared to control (positive verbal training; PVT) before extinction a) decreased CS+ negative valence during extinction and b) reduced reinstatement fear. Compared to PVT, PIT a) increased positive affect, b) decreased post-extinction CS+ negative valence, and c) reduced reinstatement responding as measured by eye blink startle reflex (when shock was used at reinstatement) and self-report fear (regardless of reinstatement US type). Results suggest that increasing positive affect prior to exposure therapy could reduce relapse through reinstatement. PMID:26073498

  20. The effect of positive mood induction on reducing reinstatement fear: Relevance for long term outcomes of exposure therapy.

    PubMed

    Zbozinek, Tomislav D; Holmes, Emily A; Craske, Michelle G

    2015-08-01

    While exposure therapy is effective in treating anxiety, fear can return after exposure. Return of fear can be understood through mechanisms of extinction learning. One form of return of fear is reinstatement, or, the fear that results from an unsignaled unconditional stimulus (US) presentation after extinction. Though the conditional response (CR; e.g., fear) typically reduces during extinction, the excitatory conditional stimulus (CS+) valence remains negative. The more negative the CS+ valence after the end of extinction, the greater the fear at reinstatement. The current study evaluated the degree to which positive mood induction (positive imagery training; PIT) compared to control (positive verbal training; PVT) before extinction a) decreased CS+ negative valence during extinction and b) reduced reinstatement fear. Compared to PVT, PIT a) increased positive affect, b) decreased post-extinction CS+ negative valence, and c) reduced reinstatement responding as measured by eye blink startle reflex (when shock was used at reinstatement) and self-report fear (regardless of reinstatement US type). Results suggest that increasing positive affect prior to exposure therapy could reduce relapse through reinstatement.

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

    PubMed

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

    2017-03-08

    Hydrogen sulfide (H2S) is an endogenous gaseous molecule that functions as a neuromodulator in the brain. We previously reported that H2S regulated amygdalar synaptic plasticity and cued fear memory in rats. However, whether endogenous H2S is required for amygdalar long-term potentiation (LTP) induction and cued fear memory formation remains unclear. Here, we show that cystathionine-β-synthase (CBS), the predominant H2S-producing enzyme in the brain, was highly expressed in the amygdala of rats. Suppressing CBS activity by inhibitor prevented activity-triggered generation of H2S in the lateral amygdala (LA) region. Incubating brain slices with CBS inhibitor significantly prevented the induction of NMDA receptors (NMDARs)-dependent LTP in the thalamo-LA pathway, and intra-LA infusion of CBS inhibitor impaired cued fear memory in rats. Notably, treatment with H2S donor, but not CBS activator, significantly reversed the impairments of LTP and fear memory caused by CBS inhibition. Mechanismly, inhibition of CBS activity led to a reduction in NMDAR-mediated synaptic response in the thalamo-LA pathway, and treatment with H2S donor restored the function of NMDARs. Collectively, these results indicate that CBS-derived H2S is required for amygdalar synaptic plasticity and cued fear memory in rats, and the effects of endogenous H2S might involve the regulation of NMDAR function.

  2. Myosin II ATPase activity mediates the long-term potentiation-induced exodus of stable F-actin bound by drebrin A from dendritic spines.

    PubMed

    Mizui, Toshiyuki; Sekino, Yuko; Yamazaki, Hiroyuki; Ishizuka, Yuta; Takahashi, Hideto; Kojima, Nobuhiko; Kojima, Masami; Shirao, Tomoaki

    2014-01-01

    The neuronal actin-binding protein drebrin A forms a stable structure with F-actin in dendritic spines. NMDA receptor activation causes an exodus of F-actin bound by drebrin A (DA-actin) from dendritic spines, suggesting a pivotal role for DA-actin exodus in synaptic plasticity. We quantitatively assessed the extent of DA-actin localization to spines using the spine-dendrite ratio of drebrin A in cultured hippocampal neurons, and found that (1) chemical long-term potentiation (LTP) stimulation induces rapid DA-actin exodus and subsequent DA-actin re-entry in dendritic spines, (2) Ca(2+) influx through NMDA receptors regulates the exodus and the basal accumulation of DA-actin, and (3) the DA-actin exodus is blocked by myosin II ATPase inhibitor, but is not blocked by myosin light chain kinase (MLCK) or Rho-associated kinase (ROCK) inhibitors. These results indicate that myosin II mediates the interaction between NMDA receptor activation and DA-actin exodus in LTP induction. Furthermore, myosin II seems to be activated by a rapid actin-linked mechanism rather than slow MLC phosphorylation. Thus the myosin-II mediated DA-actin exodus might be an initial event in LTP induction, triggering actin polymerization and spine enlargement.

  3. Intact long-term potentiation but reduced connectivity between neocortical layer 5 pyramidal neurons in a mouse model of Rett syndrome.

    PubMed

    Dani, Vardhan S; Nelson, Sacha B

    2009-09-09

    Mutations in MECP2 cause Rett syndrome and some related forms of mental retardation and autism. Mecp2-null mice exhibit symptoms reminiscent of Rett syndrome including deficits in learning. Previous reports demonstrated impaired long-term potentiation (LTP) in slices of symptomatic Mecp2-null mice, and decreased excitatory neurotransmission, but the causal relationship between these phenomena is unclear. Reduced plasticity could lead to altered transmission, or reduced excitatory transmission could alter the ability to induce LTP. To help distinguish these possibilities, we compared LTP induction and baseline synaptic transmission at synapses between layer 5 cortical pyramidal neurons in slices of wild-type and Mecp2-null mice. Paired recordings reveal that LTP induction mechanisms are intact in Mecp2-null connections, even after the onset of symptoms. However, fewer connections were found in Mecp2-null mice and individual connections were weaker. These data suggest that loss of MeCP2 function reduces excitatory synaptic connectivity and that this precedes deficits in plasticity.

  4. Long-Term Care

    MedlinePlus

    ... this page please turn Javascript on. Long-Term Care What Is Long-Term Care? Long-term care involves a variety of services ... the Escape (Esc) button on your keyboard.) Most Care Provided at Home Long-term care is provided ...

  5. The proliferative potential of human cardiac stem cells was unaffected after a long-term cryopreservation of tissue blocks

    PubMed Central

    Iguchi, Nobuo; Cho, Yasunori; Inoue, Masaki; Murakami, Tsutomu; Tabata, Minoru; Takanashi, Shuichiro; Tomoike, Hitonobu

    2017-01-01

    Background Human c-kit-positive cardiac stem cells (CSCs) have been used to treat patients suffering from ischemic cardiomyopathy. This study aimed to investigate whether a long-term storage of cardiac tissues would influence the growth potential of the subsequently isolated CSCs. Methods A total of 34 fresh samples were obtained from various cardiac regions [right atrium (RA), left atrium (LA), and/or left ventricle (LV)] of 21 patients. From 12 of these patients, 18 samples kept frozen for ~2 years were employed to prepare and characterize the CSCs. After confirming the specificity of the cell sorting by c-kit immunolabeling, the growth rate (number of doublings per day), BrdU positivity, and colony forming unit (CFU) were measured in each CSC population; the values were compared among distinct cardiac regions as well as between fresh and frozen tissues from which CSCs were derived. Results Among independent measurements indicating growth potential, the growth rate and BrdU positivity remarkably correlated in freshly prepared CSCs. The cells obtained from every examined region displayed a high proliferative capacity with the growth rate of 0.48±0.19 and the BrdU positivity of 15.0%±7.6%. The right atrial CSCs tended to show a greater growth than those in the other two areas. Similarly, the CSCs were isolated from tissue blocks, cryopreserved for ~2 years, and compared with CSCs derived from the fresh specimens of the same patients. Importantly, we were able to obtain and culture CSCs from every frozen material, and their proliferative potential, represented by the growth rate of 0.47±0.22 and the BrdU positivity of 13.7%±7.9%, was not inferior to that of the freshly prepared cells. Conclusions The long-term cryopreservation of cardiac tissues did not affect the growth potential of the derivative CSCs. Our findings should expand the therapeutic applications of these cells over a longer time span. PMID:28251120

  6. Chronic fluoxetine treatment suppresses plasticity (long-term potentiation) in the mature rodent primary auditory cortex in vivo.

    PubMed

    Dringenberg, Hans C; Branfield Day, Leora R; Choi, Deanna H

    2014-01-01

    Several recent studies have provided evidence that chronic treatment with the selective serotonin reuptake inhibitor (SSRI) fluoxetine can facilitate synaptic plasticity (e.g., ocular dominance shifts) in the adult central nervous system. Here, we assessed whether fluoxetine enhances long-term potentiation (LTP) in the thalamocortical auditory system of mature rats, a developmentally regulated form of plasticity that shows a characteristic decline during postnatal life. Adult rats were chronically treated with fluoxetine (administered in the drinking water, 0.2 mg/mL, four weeks of treatment). Electrophysiological assessments were conducted using an anesthetized (urethane) in vivo preparation, with LTP of field potentials in the primary auditory cortex (A1) induced by theta-burst stimulation of the medial geniculate nucleus. We find that, compared to water-treated control animals, fluoxetine-treated rats did not express higher levels of LTP and, in fact, exhibited reduced levels of potentiation at presumed intracortical A1 synapses. Bioactivity of fluoxetine was confirmed by a reduction of weight gain and fluid intake during the four-week treatment period. We conclude that chronic fluoxetine treatment fails to enhance LTP in the mature rodent thalamocortical auditory system, results that bring into question the notion that SSRIs act as general facilitators of synaptic plasticity in the mammalian forebrain.

  7. Dopaminergic D1 receptor agonist SKF 38393 induces GAP-43 expression and long-term potentiation in hippocampus in vivo.

    PubMed

    Williams, Shimere; Mmbaga, Natu; Chirwa, Sanika

    2006-07-10

    We evaluated whether activating dopamine D1 receptors (D1R) with an agonist will mimic the effects of long-term potentiation (LTP)-inducing electrical stimulation and trigger the expression of the presynaptic growth-associated protein 43 (GAP-43), a putative synaptic plasticity factor. Thus, we conducted GAP-43 protein analyses together with assessments of LTP across CA3/CA1 synapses in guinea pigs administered with SKF38393 (the D1R agonist) and/or SCH23390 (the D1R antagonist). Our results showed that guinea pigs treated with SKF38393 coupled with low-frequency stimulation gradually exhibited an LTP-like potentiation in correlation with increased GAP-43 protein expression. However, when SKF38393 treatment was preceded by administration of SCH23390, this antagonized the occurrence of both synaptic potentiation and GAP-43 up-regulation. By comparison, persistent LTP was readily expressed after brief high frequency tetanic stimulation in control guinea pigs, whereas animals injected with SCH23390 and tetanized only developed early-LTP but not late-LTP. Western blot analyses showed GAP-43 up-regulation in the tetanized control guinea pigs but not those injected with SCH23390. We conclude that direct D1R activations with an agonist can mimic LTP-inducing electrical stimulation to produce GAP-43 up-regulation and synaptic plasticity.

  8. Requirement of rapid Ca2+ entry and synaptic activation of metabotropic glutamate receptors for the induction of long-term depression in adult rat hippocampus

    PubMed Central

    Otani, Satoru; Connor, John A

    1998-01-01

    During block of γ-aminobutyric acid-A-mediated inhibition, low-frequency stimulation (2 Hz, 900 pulses) to Schaffer collateral-CA1 neuron synapses of adult rat hippocampus induced an N-methyl-D-aspartate receptor-independent, postsynaptic Ca2+-dependent depression of synaptic strength (long-term depression; LTD). Ratio imaging with fura-2 revealed moderate dendritic [Ca2+] increases (≈500 nM) during only the initial ≈30 s of the 7.5 min stimulation period. Conditioning for 30 s was, however, insufficient to induce LTD. The [Ca2+] changes were insensitive to the metabotropic glutamate receptor (mGluR) antagonist (+)-α-methyl-4-carboxyphenylglycine (MCPG). MCPG, however, completely blocked LTD when present during conditioning. The [Ca2+] changes were abolished by postsynaptic hyperpolarization (-110 mV at the soma). Hyperpolarizing neurons to -110 mV during conditioning significantly attenuated LTD induction. LTD induction was also blocked by the postsynaptic presence of the protein kinase C inhibitor peptide PKC(19-36). These results suggest that LTD induction in adult hippocampus by prolonged low-frequency stimulation depends on both a rapid Ca2+ influx through voltage-sensitive channels and synaptic stimulation of mGluRs which may be coupled to phospholipase C. PMID:9714858

  9. Effect of long-term removal of iron from asbestos by desferrioxamine B on subsequent mobilization by other chelators and induction of DNA single-strand breaks.

    PubMed

    Chao, C C; Aust, A E

    1994-01-01

    The long-term removal of iron from crocidolite or amosite by desferrioxamine B (DF) at pH 7.5 or 5.0 was studied. Crocidolite or amosite (1 mg/ml) was suspended in 50 mM NaCl at pH 7.5 or 5.0 with the addition of 1 mM DF for up to 90 days. Although the rate of iron mobilization decreased with time, iron was continuously mobilized from both forms of asbestos at pH 5.0 or 7.5. The amount of iron mobilized from crocidolite was at least twice that mobilized from amosite at either pH. Iron was mobilized more rapidly from crocidolite at pH 5.0 than at 7.5 for the first 15 days, but at later times the amount being mobilized at pH 7.5 became equal to or slightly greater than that at 5.0. For amosite, the mobilization at pH 5.0 was always greater than that at pH 7.5. Next, the effect of iron removal from asbestos by DF on subsequent iron mobilization by a second chelator (EDTA or citrate) and on induction of DNA single-strand breaks (SSBs) was studied. Asbestos, treated for up to 15 days with DF at pH 7.5, was washed to remove ferrioxamine and excess DF, then incubated with EDTA or citrate (1 mM). The rates of iron mobilization from both forms of asbestos by a second chelator decreased as more and more iron was removed by DF. Induction of DNA SSBs also decreased, reflecting the unavailability of iron to catalyze the damage. The results suggest three things. First, if long-term mobilization of iron from asbestos occurs in vivo as has been observed in vitro, it may play a role in the long-term biological effects of asbestos. Second, more rapid mobilization of iron from asbestos fibers may occur when the fibers are phagocytized by cells and maintained in phagosomes where the pH is 4.0-5.0. Third, treatment of asbestos by iron chelators, such as DF, prior to exposure to cultured cells or whole animals, may reduce the biological effects of asbestos resulting from iron, but may not completely eliminate them.

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

    PubMed

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

    2015-05-01

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

  11. Inhibition of fatty acid amide hydrolase (FAAH) reduces spinal nociceptive responses and expression of spinal long-term potentiation (LTP).

    PubMed

    Eriksen, Guro S; Jacobsen, Line Melå; Mahmood, Aqsa; Pedersen, Linda M; Gjerstad, Johannes

    2012-02-10

    Fatty acid amide hydrolase (FAAH) is an enzyme that metabolizes endocannabinoids and fatty acid amides possibly linked to activation of the opioid system. To examine how this enzyme affects spinal signalling, electrophysiological recordings in the dorsal horn and qPCR on dorsal horn tissue following systemic administration of the FAAH inhibitor URB597 (0.3 and 1.0mg/kg i.v.) and spinal administration of the opioid receptor antagonist naloxone (0.1 μg/μl i.th.), were performed. The present data showed that the suppressive effect of the FAAH inhibitor URB597 (1.0mg/kg i.v.) on the spinal nociceptive responses was prevented by spinal administration of the opioid receptor antagonist naloxone (0.1 μg/μl i.th.). Moreover, the present findings demonstrated that the FAAH inhibitor URB597 (1.0mg/kg i.v.) partly reversed expression of spinal long-term potentiation (LTP) and also attenuated the LTP-associated increased Zif expression. We conclude that pharmacological inactivation of FAAH may be a promising strategy to inhibit the development of central hyperalgesia; thereby reinforcing the role of FAAH as a potential therapeutic target.

  12. Enhancement of Glutamate Release by l-Fucose Changes Effects of Glutamate Receptor Antagonists on Long-Term Potentiation in the Rat Hippocampus

    PubMed Central

    Matthies, Henry; Schroeder, Helmut; Smalla, Karl-Heinz; Krug, Manfred

    2000-01-01

    In previous studies l-fucose has been shown to facilitate long-term memory formation and to enhance and prolong long-term potentiation (LTP). To search for possible presynaptic or postsynaptic mechanisms that are affected by l-fucose, we examined the effect of l-fucose on (1) inhibition of LTP induction via glutamate receptors by antagonists, (2) paired-pulse facilitation, and (3) presynaptic transmitter release. Coapplication of 0.2 mm l-fucose with the competitive N-methyl-d-aspartate (NMDA) receptor antagonist, d-2-amino-5-phosphonovalerate (AP5), or coapplication of 0.2 mml-fucose in the presence of an inhibitor for class I/II metabotropic glutamate receptors, (S)-α-methyl-4-carboxyphenylglycine (MCPG), reversed LTP blockade in the CA1-region of hippocampal slices. In contrast, l-fucose had no effect on the LTP blockade by the noncompetitive NMDA ion-channel blocker (5R,10S)-(+)-5-Methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5, 10-imine hydrogen maleate (MK-801). Paired-pulse facilitation, which is a primarily presynaptic phenomenon of short-term plasticity, was decreased in the presence of 0.2 mm l-fucose. Furthermore, l-fucose enhanced the K+-stimulated release of [3H]-d-aspartate from preloaded hippocampal slices in a concentration-dependent manner. These observations demonstrate an influence of l-fucose on transmitter release that in turn can increase transmitter availability at postsynaptic glutamate receptors. This effect of l-fucose may contribute to the LTP facilitation seen in vitro and in vivo as well as to improvement in memory formation. PMID:10940323

  13. Presynaptic long-term plasticity

    PubMed Central

    Yang, Ying; Calakos, Nicole

    2013-01-01

    Long-term synaptic plasticity is a major cellular substrate for learning, memory, and behavioral adaptation. Although early examples of long-term synaptic plasticity described a mechanism by which postsynaptic signal transduction was potentiated, it is now apparent that there is a vast array of mechanisms for long-term synaptic plasticity that involve modifications to either or both the presynaptic terminal and postsynaptic site. In this article, we discuss current and evolving approaches to identify presynaptic mechanisms as well as discuss their limitations. We next provide examples of the diverse circuits in which presynaptic forms of long-term synaptic plasticity have been described and discuss the potential contribution this form of plasticity might add to circuit function. Finally, we examine the present evidence for the molecular pathways and cellular events underlying presynaptic long-term synaptic plasticity. PMID:24146648

  14. In-Situ Strain Analysis of Potential Habitat Composites Exposed to a Simulated Long-Term Lunar Radiation Exposure

    NASA Technical Reports Server (NTRS)

    Rojdev, Kristina; O'Rourke, Mary Jane; Hill, Charles; Nutt, Steven; Atwell, William

    2010-01-01

    NASA is studying the effects of long-term space radiation on potential multifunctional composite materials for habitats to better determine their characteristics in the harsh space environment. Two composite materials were selected for the study and were placed in a test stand that simulated the stresses of a pressure vessel wall on the material. The samples in the test stand were exposed to radiation at either a fast dose rate or a slow dose rate, and their strain and temperature was recorded during the exposure. It was found that during a fast dose rate exposure the materials saw a decreased strain with time, or a shrinking of the materials. Given previous radiation studies of polymers, this is believed to be a result of crosslinking occurring in the matrix material. However, with a slow dose rate, the materials saw an increase in strain with time, or a stretching of the materials. This result is consistent with scission or degradation of the matrix occurring, possibly due to oxidative degradation.

  15. Receptor protein tyrosine phosphatase α is essential for hippocampal neuronal migration and long-term potentiation

    PubMed Central

    Petrone, Angiola; Battaglia, Fortunato; Wang, Cheng; Dusa, Adina; Su, Jing; Zagzag, David; Bianchi, Riccardo; Casaccia-Bonnefil, Patrizia; Arancio, Ottavio; Sap, Jan

    2003-01-01

    Despite clear indications of their importance in lower organisms, the contributions of protein tyrosine phosphatases (PTPs) to development or function of the mammalian nervous system have been poorly explored. In vitro studies have indicated that receptor protein tyrosine phosphatase α (RPTPα) regulates SRC family kinases, potassium channels and NMDA receptors. Here, we report that absence of RPTPα compromises correct positioning of pyramidal neurons during development of mouse hippocampus. Thus, RPTPα is a novel member of the functional class of genes that control radial neuronal migration. The migratory abnormality likely results from a radial glial dysfunction rather than from a neuron-autonomous defect. In spite of this aberrant development, basic synaptic transmission from the Schaffer collateral pathway to CA1 pyramidal neurons remains intact in Ptpra–/– mice. However, these synapses are unable to undergo long-term potentiation. Mice lacking RPTPα also underperform in the radial-arm water-maze test. These studies identify RPTPα as a key mediator of neuronal migration and synaptic plasticity. PMID:12912911

  16. Enhanced perisomatic inhibition and impaired long-term potentiation in the CA1 region of juvenile CHL1-deficient mice.

    PubMed

    Nikonenko, Alexander G; Sun, Mu; Lepsveridze, Eka; Apostolova, Ivayla; Petrova, Iveta; Irintchev, Andrey; Dityatev, Alexander; Schachner, Melitta

    2006-04-01

    The cell adhesion molecule, CHL1, like its close homologue L1, is important for normal brain development and function. In this study, we analysed the functional role of CHL1 in synaptic transmission in the CA1 region of the hippocampus using juvenile CHL1-deficient (CHL1-/-) and wild-type (CHL1+/+) mice. Inhibitory postsynaptic currents evoked in pyramidal cells by minimal stimulation of perisomatically projecting interneurons were increased in CHL1-/- mice compared with wild-type littermates. Also, long-term potentiation (LTP) at CA3-CA1 excitatory synapses was reduced under physiological conditions in CHL1-/- mice. This abnormality was abolished by application of a GABAA receptor antagonist, suggesting that enhanced inhibition is the cause of LTP impairment. Quantitative ultrastructural and immunohistochemical analyses revealed aberrations possibly related to the abnormally high inhibition observed in CHL1-/- mice. The length and linear density of active zones in symmetric synapses on pyramidal cell bodies, as well as number of perisomatic puncta containing inhibitory axonal markers were increased. Density and total number of parvalbumin-positive interneurons was also abnormally high. These observations and the finding that CA1 interneurons express CHL1 protein indicate that CHL1 is important for regulation of inhibitory synaptic transmission and interneuron populations in the postnatal brain. The observed enhancement of inhibitory transmission in CHL1-/- mice is in contrast to the previous finding of reduced inhibition in L1 deficient mice and indicates different functions of these two closely related molecules.

  17. Long-term characterization, lagoon treatment and migration potential of landfill leachate: a case study in an active Italian landfill.

    PubMed

    Frascari, D; Bronzini, F; Giordano, G; Tedioli, G; Nocentini, M

    2004-01-01

    The elaboration of 10 years of monitoring of leachate quality and quantity, leachate treatment and degree of contamination of soil and surface waters at the Tre Monti site--an active, 4-million-m(3) landfill in Northern Italy--is presented in this study. A hydrological model of leachate production is applied, with a good match of the experimental data. The concentrations of all leachate components except sulfate are characterized by fluctuations over a constant or increasing value. Different ways of interpreting leachate quality data are discussed; the elaboration indicates that the pollutant load on the leachate treatment facility will remain basically constant as long as waste will be added to the landfill. The analysis of the data relative to 10 years of leachate pre-treatment in the adjoining, non-aerated lagoon system indicates that a significant removal is achieved for most leachate components; the operational conditions of the plant are described, and the removal mechanisms are discussed. Finally, the potential for contamination of soil and surface waters is examined by analyzing long-term quality trends of the sub-superficial waters sampled near the lagoons and by means of an analytical campaign conducted on clay cores sampled near and underneath the treatment ponds. The experimental values indicate that the clay layer located under the entire site offers an effective barrier to the migration of leachate contaminants.

  18. Involvement of protein kinase ζ in the maintenance of hippocampal long-term potentiation in rats with chronic visceral hypersensitivity

    PubMed Central

    Chen, Aiqin; Bao, Chengjia; Tang, Ying; Luo, Xiaoqing; Guo, Lixia; Liu, Bin

    2015-01-01

    The hippocampal long-term potentiation (LTP) was implicated in the formation of visceral hypersensitivity in rats with irritable bowel syndrome in our previous study. Recent studies have shown that protein kinase M ζ (PKMζ) may be responsible for the maintenance of LTP in memory formation. However, it remains unclear whether PKMζ is involved in the visceral hypersensitivity. In this study, a rat model of visceral hypersensitivity was generated by neonatal maternal separation (NMS). The visceral hypersensitivity was assessed by recording responses of the external oblique abdominal muscle to colorectal distension. Our results demonstrated that hippocampal LTP and visceral hypersensitivity were enhanced significantly in rats of NMS. ζ-Pseudosubstrate inhibitory peptide (ZIP) could dose dependently inhibit the maintenance of Cornu Ammonis area 1 LTP in rats of NMS. Furthermore, Western blot data showed that the expression of hippocampal phosphorylated PKMζ (p-PKMζ) significantly increased in rats of NMS. In addition, bilateral intrahippocampal injections of ZIP attenuated the visceral hypersensitivity dose dependently in rats of NMS. The maximal inhibition was observed at 30 min, and significant inhibition lasted for 1.5–2 h after ZIP application. Besides, data from the open-field test and Morris water maze showed that ZIP did not influence the movement and spatial procedural memory in rats of NMS. In conclusion, p-PKMζ might be a critical protein in the maintenance of hippocampal LTP, which could result in visceral hypersensitivity. PMID:25761958

  19. Involvement of protein kinase ζ in the maintenance of hippocampal long-term potentiation in rats with chronic visceral hypersensitivity.

    PubMed

    Chen, Aiqin; Bao, Chengjia; Tang, Ying; Luo, Xiaoqing; Guo, Lixia; Liu, Bin; Lin, Chun

    2015-05-01

    The hippocampal long-term potentiation (LTP) was implicated in the formation of visceral hypersensitivity in rats with irritable bowel syndrome in our previous study. Recent studies have shown that protein kinase M ζ (PKMζ) may be responsible for the maintenance of LTP in memory formation. However, it remains unclear whether PKMζ is involved in the visceral hypersensitivity. In this study, a rat model of visceral hypersensitivity was generated by neonatal maternal separation (NMS). The visceral hypersensitivity was assessed by recording responses of the external oblique abdominal muscle to colorectal distension. Our results demonstrated that hippocampal LTP and visceral hypersensitivity were enhanced significantly in rats of NMS. ζ-Pseudosubstrate inhibitory peptide (ZIP) could dose dependently inhibit the maintenance of Cornu Ammonis area 1 LTP in rats of NMS. Furthermore, Western blot data showed that the expression of hippocampal phosphorylated PKMζ (p-PKMζ) significantly increased in rats of NMS. In addition, bilateral intrahippocampal injections of ZIP attenuated the visceral hypersensitivity dose dependently in rats of NMS. The maximal inhibition was observed at 30 min, and significant inhibition lasted for 1.5-2 h after ZIP application. Besides, data from the open-field test and Morris water maze showed that ZIP did not influence the movement and spatial procedural memory in rats of NMS. In conclusion, p-PKMζ might be a critical protein in the maintenance of hippocampal LTP, which could result in visceral hypersensitivity.

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

    PubMed

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

    2013-06-01

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

  1. The Rapid Effect of Bisphenol-A on Long-Term Potentiation in Hippocampus Involves Estrogen Receptors and ERK Activation

    PubMed Central

    Chen, Xiaowei; Wang, Yu; Xu, Fang; Wei, Xiaofei; Zhang, Junfang; Wang, Chuang; Wei, Hua; Xu, Shujun; Yan, Peiyun; Zhou, Wenhua; Mody, Istvan

    2017-01-01

    Bisphenol-A (BPA), a widely used synthetic compound in plastics, disrupts endocrine function and interferes with physiological actions of endogenous gonadal hormones. Chronic effects of BPA on reproductive function, learning and memory, brain structure, and social behavior have been intensively investigated. However, less is known about the influence of BPA on long-term potentiation (LTP), one of the major cellular mechanisms that underlie learning and memory. In the present study, for the first time we investigated the effect of different doses of BPA on hippocampal LTP in rat brain slices. We found a biphasic effect of BPA on LTP in the dentate gyrus: exposure to BPA at a low dose (100 nM) enhanced LTP and exposure to BPA at a high dose (1000 nM) inhibited LTP compared with vehicle controls. The rapid facilitatory effect of low-dose BPA on hippocampal LTP required membrane-associated estrogen receptor (ER) and involved activation of the extracellular signal-regulated kinase (ERK) signaling pathway. Coadministration of 17β-estradiol (E2, the primary estrogen hormone) and BPA (100 nM) abolished both the BPA-induced enhancement of LTP and the E2-induced enhancement of baseline fEPSP, suggesting a complex interaction between BPA- and E2-mediated signaling pathways. Our investigation implies that even nanomolar levels of endocrine disrupters (e.g., BPA) can induce significant effects on hippocampal LTP. PMID:28255459

  2. Long-term monitoring of airborne nickel (Ni) pollution in association with some potential source processes in the urban environment.

    PubMed

    Kim, Ki-Hyun; Shon, Zang-Ho; Mauulida, Puteri T; Song, Sang-Keun

    2014-09-01

    The environmental behavior and pollution status of nickel (Ni) were investigated in seven major cities in Korea over a 13-year time span (1998-2010). The mean concentrations of Ni measured during the whole study period fell within the range of 3.71 (Gwangju: GJ) to 12.6ngm(-3) (Incheon: IC). Although Ni values showed a good comparability in a relatively large spatial scale, its values in most cities (6 out of 7) were subject to moderate reductions over the study period. To assess the effect of major sources on the long-term distribution of Ni, the relationship between their concentrations and the potent source processes like non-road transportation sources (e.g., ship and aircraft emissions) were examined from some cities with port and airport facilities. The potential impact of long-range transport of Asian dust particles in controlling Ni levels was also evaluated. The overall results suggest that the Ni levels were subject to gradual reductions over the study period irrespective of changes in such localized non-road source activities. The pollution of Ni at all the study sites was maintained well below the international threshold (Directive 2004/107/EC) value of 20ngm(-3).

  3. Matrix Metalloproteinases Regulate the Formation of Dendritic Spine Head Protrusions during Chemically Induced Long-Term Potentiation

    PubMed Central

    Szepesi, Zsuzsanna; Bijata, Monika; Ruszczycki, Blazej; Kaczmarek, Leszek; Wlodarczyk, Jakub

    2013-01-01

    Dendritic spines are are small membranous protrusions that extend from neuronal dendrites and harbor the majority of excitatory synapses. Increasing evidence has shown that matrix metalloproteinases (MMPs), a family of extracellularly acting and Zn2+-dependent endopeptidases, are able to rapidly modulate dendritic spine morphology. Spine head protrusions (SHPs) are filopodia-like processes that extend from the dendritic spine head, representing a form of postsynaptic structural remodeling in response to altered neuronal activity. Herein, we show that chemically induced long-term potentiation (cLTP) in dissociated hippocampal cultures upregulates MMP-9 activity that controls the formation of SHPs. Blocking of MMPs activity or microtubule dynamics abolishes the emergence of SHPs. In addition, autoactive recombinant MMP-9, promotes the formation of SHPs in organotypic hippocampal slices. Furthermore, spines with SHPs gained postsynaptic α-amino-3-hydroxyl-5-methyl-4-isoxazole propionic acid (AMPA) receptors upon cLTP and the synaptic delivery of AMPA receptors was controlled by MMPs. The present results strongly imply that MMP-9 is functionally involved in the formation of SHPs and the control of postsynaptic receptor distribution upon cLTP. PMID:23696812

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

    PubMed Central

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

    2014-01-01

    Prolonged and severe stress leads to cognitive deficits, but facilitates emotional behaviour. Little is known about the synaptic basis for this contrast. Here, we report that in rats subjected to chronic immobilization stress, long-term potentiation (LTP) and NMDA receptor (NMDAR)-mediated synaptic responses are enhanced in principal neurons of the lateral amygdala, a brain area involved in fear memory formation. This is accompanied by electrophysiological and morphological changes consistent with the formation of ‘silent synapses’, containing only NMDARs. In parallel, chronic stress also reduces synaptic inhibition. Together, these synaptic changes would enable amygdalar neurons to undergo further experience-dependent modifications, leading to stronger fear memories. Consistent with this prediction, stressed animals exhibit enhanced conditioned fear. Hence, stress may leave its mark in the amygdala by generating new synapses with greater capacity for plasticity, thereby creating an ideal neuronal substrate for affective disorders. These findings also highlight the unique features of stress-induced plasticity in the amygdala that are strikingly different from the stress-induced impairment of structure and function in the hippocampus. PMID:24298153

  5. Humans with Type-2 Diabetes Show Abnormal Long-Term Potentiation-Like Cortical Plasticity Associated with Verbal Learning Deficits

    PubMed Central

    Fried, Peter J.; Schilberg, Lukas; Brem, Anna-Katharine; Saxena, Sadhvi; Wong, Bonnie; Cypess, Aaron M.; Horton, Edward S.; Pascual-Leone, Alvaro

    2016-01-01

    Background Type-2 diabetes mellitus (T2DM) accelerates cognitive aging and increases risk of Alzheimer’s disease. Rodent models of T2DM show altered synaptic plasticity associated with reduced learning and memory. Humans with T2DM also show cognitive deficits, including reduced learning and memory, but the relationship of these impairments to the efficacy of neuroplastic mechanisms has never been assessed. Objective Our primary objective was to compare mechanisms of cortical plasticity in humans with and without T2DM. Our secondary objective was to relate plasticity measures to standard measures of cognition. Methods A prospective cross-sectional cohort study was conducted on 21 adults with T2DM and 15 demographically-similar non-diabetic controls. Long-term potentiation-like plasticity was assessed in primary motor cortex by comparing the amplitude of motor evoked potentials (MEPs) from single-pulse transcranial magnetic stimulation before and after intermittent theta-burst stimulation (iTBS). Plasticity measures were compared between groups and related to neuropsychological scores. Results In T2DM, iTBS-induced modulation of MEPs was significantly less than controls, even after controlling for potential confounds. Furthermore, in T2DM, modulation of MEPs 10-min post-iTBS was significantly correlated with Rey Auditory Verbal Learning Task (RAVLT) performance. Conclusion Humans with T2DM show abnormal cortico-motor plasticity that is correlated with reduced verbal learning. Since iTBS after-effects and the RAVLT are both NMDA receptor-dependent measures, their relationship in T2DM may reflect brain-wide alterations in the efficacy of NMDA receptors. These findings offer novel mechanistic insights into the brain consequences of T2DM and provide a reliable means to monitor brain health and evaluate the efficacy of clinical interventions. PMID:27636847

  6. Differential contribution of BDNF and NGF to long-term potentiation in the superior cervical ganglion of the rat.

    PubMed

    Arias, Erwin R; Valle-Leija, Pablo; Morales, Miguel A; Cifuentes, Fredy

    2014-06-01

    Synaptic transmission in the sympathetic nervous system is a plastic process modulated by different factors. We characterized the effects of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) on basal transmission and ganglionic long-term potentiation (LTP) in the rat superior cervical ganglion. LTP was elicited by supramaximal tetanic stimulation (40 Hz, 3 s) of the sympathetic trunk and was quantified by measuring LTP decay time and LTP extent. Neurotrophins did not affect basal transmission, however, they differentially affected LTP. BDNF (200 ng/ml) increased LTP decay time and LTP extent 2.0-fold (p < 0.01). In contrast, NGF showed a dual effect: 200 ng/ml NGF reduced LTP decay time and LTP extent to 53% and to 32% of control value (p < 0.0001 and p < 0.02; respectively), whereas >350 ng/ml NGF significantly increased LTP decay time and LTP extent (p < 0.02). Digital analysis of compound action potentials suggests that neurotrophins could change the synchronization of unitary action potentials. Pharmacological data obtained in intact ganglia show that C2-ceramide produced a 2-fold enhancement in LTP, whereas tyrphostin AG879, an inhibitor of tyrosine kinase activity, reversed the NGF blockade and produced by itself an enhancement in LTP. In sliced ganglia we observed that an anti-TrkA antibody reversed the NGF-induced LTP blockade. Immunohistochemistry studies revealed that 83% of ganglionic neurons express TrkA, whereas 52% express p75 receptor, and 18% express TrkB receptor. We propose that p75 neurotrophin receptors and probably TrkB signaling enhance LTP, whereas TrkA signaling reduces it.

  7. Synaptic plasticity deficits in an experimental model of rett syndrome: long-term potentiation saturation and its pharmacological reversal.

    PubMed

    Weng, S-M; McLeod, F; Bailey, M E S; Cobb, S R

    2011-04-28

    Rett syndrome (RTT), a disorder caused almost exclusively by mutations in the X-linked gene, MECP2, has a phenotype thought to be primarily of neurological origin. Disruption of Mecp2 in mice results in a prominent RTT-like phenotype. One of the consequences of MeCP2 absence in the brain is altered functional and structural plasticity. We aimed to characterize synaptic effects related to plasticity in the hippocampus further and establish whether plasticity defects are amenable to pharmacological reversal. Using male mice in which Mecp2 expression was prevented by a stop cassette, we assessed synaptic plasticity in area CA1 at different phenotypic stages, scoring the mice weekly for overt RTT-like signs. Strongly symptomatic Mecp2(stop/y) mice displayed reduced long-term potentiation (LTP, 40.2±1.6% of wild-type), post-tetanic potentiation (PTP, 45±18.8% of wild-type) and paired-pulse facilitation (PPF, 78±0.1% of wild type) (all P<0.05), the impairment increasing with symptom severity score. These plasticity impairments were absent in presymptomatic mice. Repeated high frequency stimulation revealed pronounced LTP saturation in symptomatic Mecp2(stop/y) mice, suggesting an LTP 'ceiling' effect. Bath application of the weak NMDA receptor blocker memantine (1 μM) resulted in partial restoration of a short-term plasticity component. These data support that idea that progressive functional synaptic impairment is a key feature in the RTT brain and demonstrate the potential for the pharmacological restoration of plasticity function.

  8. Sex differences in hippocampal long-term potentiation (LTP) and Pavlovian fear conditioning in rats: positive correlation between LTP and contextual learning.

    PubMed

    Maren, S; De Oca, B; Fanselow, M S

    1994-10-24

    Three experiments investigated sex differences in hippocampal long-term potentiation (LTP) and Pavlovian fear conditioning in rats. Experiment 1 revealed a robust sex difference in the magnitude of LTP induced at perforant path synapses in the dentate gyrus of pentobarbital-anesthetized rats. This sex difference in LTP was evident in rats of 35 and 60 days of age and was not the result of pre-LTP sex differences in perforant path synaptic transmission; 20-day-old rats did not show LTP. An analysis of field potentials evoked during LTP induction revealed a sex difference in the magnitude of N-methyl-D-aspartate (NMDA) receptor activation that was highly correlated with the magnitude of LTP. Experiment 2 showed that males condition more fear, measured as freezing, to the contextual conditional stimuli (CSs) of a conditioning chamber compared to their female counterparts. This sex difference in conditional freezing was apparent with both low and high unconditional stimulus (US, footshock) intensities. Experiment 3 revealed that the enhanced fear conditioning in males was specific to contextual CSs, and consisted of a more rapid rate of conditioning. Together, these experiments reveal a positive correlation between the magnitude of hippocampal LTP and a form of learning that depends on the hippocampus. Furthermore, they suggest a neural basis for sex differences in hippocampus-dependent learning tasks.

  9. Long-term quality of life after intensified multi-modality treatment of oral cancer including intra-arterial induction chemotherapy and adjuvant chemoradiation

    PubMed Central

    Kovács, Adorján F.; Stefenelli, Ulrich; Thorn, Gerrit

    2015-01-01

    Background: Quality of life (QoL) studies are well established when accompanying trials in head and neck cancer, but studies on long-term survivors are rare. Aims: The aim was to evaluate long-term follow-up patients treated with an intensified multi-modality therapy. Setting and Design: Cross-sectional study, tertiary care center. Patients and Methods: A total of 135 oral/oropharyngeal cancer survivors having been treated with an effective four modality treatment (intra-arterial induction chemotherapy, radical surgery, adjuvant radiation, concurrent systemic chemotherapy) filled European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and HN35 questionnaires. Mean distance to treatment was 6.1 (1.3–16.6) years. Results were compared with a reference patient population (EORTC reference manual). In-study group comparison was also carried out. Statistical Analysis: One-sample t-test, Mann–Whitney-test, Kruskal–Wallis analysis. Results: QoL scores of both populations were well comparable. Global health status, cognitive and social functioning, fatigue, social eating, status of teeth, mouth opening and dryness, and sticky saliva were significantly worse in the study population; pain and need for pain killers, cough, need for nutritional support, problems with weight loss and gain were judged to be significantly less. Patients 1-year posttreatment had generally worse scores as compared to patients with two or more years distance to treatment. Complex reconstructive measures and adjuvant (chemo) radiation were main reasons for significant impairment of QoL. Conclusion Subjective disease status of patients following a maximized multi-modality treatment showed an expectable high degree of limitations, but was generally comparable to a reference group treated less intensively, suggesting that the administration of an intensified multi-modality treatment is feasible in terms of QoL/effectivity ratio. PMID:26389030

  10. The effect of age on the homotopic motor cortical long-term potentiation-like effect induced by quadripulse stimulation.

    PubMed

    Hanajima, Ritsuko; Tanaka, Nobuyuki; Tsutsumi, Ryosuke; Enomoto, Hiroyuki; Abe, Mitsunari; Nakamura, Koichiro; Kobayashi, Shunsuke; Hamada, Masashi; Shimizu, Takahiro; Terao, Yasuo; Ugawa, Yoshikazu

    2017-04-06

    The reduction of plasticity with age has been shown by many previous papers in animal experiments. This issue can be studied in humans because several non-invasive brain stimulation techniques induce synaptic plasticity in the human brain. We investigated the influence of individuals' age on the responder rate of the long-term potentiation (LTP)-like effect induced by quadripulse magnetic stimulation (QPS). The participants were 107 healthy volunteers: 53 older participants (Mean ± SD 65.0 ± 1.5 years) and 54 younger participants (37.2 ± 8.7). The quadripulse stimulation with 5-ms inter-pulse interval (QPS5) was applied over the primary motor cortex (M1). We measured motor evoked potentials (MEPs) before QPS, and at five time points after QPS for up to 25 min. In each participant, average MEP amplitude (size) ratios were quantified. We first classified participants as responders and non-responders simply by comparing the size ratio with 1.0 for consistency with previous studies, then as "significant responders", "non-responders", and "opposite responders" for more detailed analysis by comparing the size ratio with the mean and standard deviation of the MEP size ratios of the sham condition. The degree of LTP-like effects induced by QPS5 was significantly smaller in the older group compared to the younger group. Also, the rates of responders and significant responders were lower in the older group (58 and 47%, respectively) compared to the younger group (80 and 76%, respectively). The age of the participants significantly affected the LTP-like effect induced by QPS5, which suggests that brain plasticity decreases with age.

  11. Hippocampal NR2B-containing NMDA receptors enhance long-term potentiation in rats with chronic visceral pain.

    PubMed

    Chen, Yu; Chen, Ai-qin; Luo, Xiao-qing; Guo, Li-xia; Tang, Ying; Bao, Cheng-jia; Lin, Ling; Lin, Chun

    2014-06-27

    Pain and learning memory have striking similarities in synaptic plasticity. Activation of the N-methyl-D-aspartic acid receptors 2B subunits (NR2B-NMDAs) is responsible for the hippocampal LTP in memory formation. In our previous studies, we found the significant enhancement of CA1 hippocampal long-term potentiation (LTP) induced by high-frequency stimulation (HFS) in rats with chronic visceral pain. However, it is unclear whether the NR2B-NMDAs are required for the LTP in chronic visceral pain. In this study, a rat model with irritable bowel syndrome (IBS) was established by colorectal distention (CRD). The sensitivity of visceral pain and HFS-induced LTP at SC-CA1 synapses were significantly enhanced in IBS-like rats (p<0.05). In addition, hippocampal NR2B protein levels significantly increased in IBS-like rats (p<0.05). To test whether NR2B-NMDAs are responsible for the LTP, effects of Ro 25-6981, a selective antagonist of NR2B-NMDAs, on field potential in CA1 region were investigated in vitro. Our results demonstrated that Ro 25-6981 dose-dependently inhibited the facilitation of CA1 LTP in IBS-like rats. The plausible activation mechanism of hippocampal NR2B-NMDAs in the LTP enhancement was further explored. Western blot data indicated that expression of tyrosine phosphorylated NR2B protein in hippocampus significantly enhanced in IBS-like rats. Accordingly, genistein, a specific inhibitor of tyrosine kinases, dose-dependently blocked the facilitation of hippocampal LTP in IBS-like rats. Furthermore, EMG data revealed that intra-hippocampal injection of Ro 25-6981 dose-dependently attenuated the visceral hypersensitivity. In conclusion, hippocampal NR2B-NMDAs are responsible for the facilitation of CA1 LTP via tyrosine phosphorylation, which leads to visceral hypersensitivity.

  12. Estimating long-term regional groundwater recharge for the evaluation of potential solution alternatives to waterlogging and salinisation

    NASA Astrophysics Data System (ADS)

    Singh, Ajay

    2011-09-01

    SummaryAccurate estimation of the groundwater recharge is essential for efficient and sustainable groundwater management in arid and semi-arid regions, as water resources are critical to economic development in these areas. Various techniques are available to quantify recharge. The hydrological budget model proposed herein is unique, simple, and easy to apply. It uses data on groundwater level, groundwater extraction, and distributed specific yield information for estimating groundwater recharge. The Model is employed to estimate the seasonal long-term (35 years, e.g., from 1974 to 2009) groundwater recharge of an irrigated semi-arid area located in Haryana State of India, where groundwater levels are rising, continuously. The results are analysed to provide an overview of the process dynamics that led to imbalance of the system. Groundwater recharge analysis during the study period reveals that percolation from irrigated fields is the main recharge component with 49% contribution to the total recharge. An annual groundwater table rise of 0.14 m has been estimated for the study area. Various potential solution alternatives are evaluated to mitigate the problems of waterlogging and salinisation, considering the socio-economic issues which have wider policy significance on sustainability. Several suitable water management strategies such as reduction in rice area, increase in pumping volume and using the groundwater conjunctively with higher quality canal water, and lining of canal networks are suggested to bring the watertable down to a safe limit and to prevent further rising of the watertable. Among the potential solution alternatives studied, the one which considers 10% reduction in rice area along with 2% increase in pumping volume and 20% canal lining, yields best result for mitigating the waterlogging problems.

  13. ErbB4 in parvalbumin-positive interneurons is critical for neuregulin 1 regulation of long-term potentiation.

    PubMed

    Chen, Yong-Jun; Zhang, Meng; Yin, Dong-Min; Wen, Lei; Ting, Annie; Wang, Pu; Lu, Yi-Sheng; Zhu, Xin-Hong; Li, Shu-Ji; Wu, Cui-Ying; Wang, Xue-Ming; Lai, Cary; Xiong, Wen-Cheng; Mei, Lin; Gao, Tian-Ming

    2010-12-14

    Neuregulin 1 (NRG1) is a trophic factor that acts by stimulating ErbB receptor tyrosine kinases and has been implicated in neural development and synaptic plasticity. In this study, we investigated mechanisms of its suppression of long-term potentiation (LTP) in the hippocampus. We found that NRG1 did not alter glutamatergic transmission at SC-CA1 synapses but increased the GABA(A) receptor-mediated synaptic currents in CA1 pyramidal cells via a presynaptic mechanism. Inhibition of GABA(A) receptors blocked the suppressing effect of NRG1 on LTP and prevented ecto-ErbB4 from enhancing LTP, implicating a role of GABAergic transmission. To test this hypothesis further, we generated parvalbumin (PV)-Cre;ErbB4(-/-) mice in which ErbB4, an NRG1 receptor in the brain, is ablated specifically in PV-positive interneurons. NRG1 was no longer able to increase inhibitory postsynaptic currents and to suppress LTP in PV-Cre;ErbB4(-/-) hippocampus. Accordingly, contextual fear conditioning, a hippocampus-dependent test, was impaired in PV-Cre;ErbB4(-/-) mice. In contrast, ablation of ErbB4 in pyramidal neurons had no effect on NRG1 regulation of hippocampal LTP or contextual fear conditioning. These results demonstrate a critical role of ErbB4 in PV-positive interneurons but not in pyramidal neurons in synaptic plasticity and support a working model that NRG1 suppresses LTP by enhancing GABA release. Considering that NRG1 and ErbB4 are susceptibility genes of schizophrenia, these observations contribute to a better understanding of how abnormal NRG1/ErbB4 signaling may be involved in the pathogenesis of schizophrenia.

  14. Grazing management contributions to net global warming potential: a long-term evaluation in the Northern Great Plains.

    PubMed

    Liebig, M A; Gross, J R; Kronberg, S L; Phillips, R L; Hanson, J D

    2010-01-01

    The role of grassland ecosystems as net sinks or sources of greenhouse gases (GHGs) is limited by a paucity of information regarding management impacts on the flux of nitrous oxide (N(2)O) and methane (CH(4)). Furthermore, no long-term evaluation of net global warming potential (GWP) for grassland ecosystems in the northern Great Plains (NGP) of North America has been reported. Given this need, we sought to determine net GWP for three grazing management systems located within the NGP. Grazing management systems included two native vegetation pastures (moderately grazed pasture [MGP], heavily grazed pasture [HGP]) and a heavily grazed crested wheatgrass [Agropyron desertorum (Fisch. ex. Link) Schult.] pasture (CWP) near Mandan, ND. Factors evaluated for their contribution to GWP included (i) CO(2) emissions associated with N fertilizer production and application, (ii) literature-derived estimates of CH(4) production for enteric fermentation, (iii) change in soil organic carbon (SOC) over 44 yr using archived soil samples, and (iv) soil-atmosphere N(2)O and CH(4) fluxes over 3 yr using static chamber methodology. Analysis of SOC indicated all pastures to be significant sinks for SOC, with sequestration rates ranging from 0.39 to 0.46 Mg C ha(-1) yr(-1). All pastures were minor sinks for CH(4) (<2.0 kg CH(4)-C ha(-1) yr(-1)). Greater N inputs within CWP contributed to annual N(2)O emission nearly threefold greater than HGP and MGP. Due to differences in stocking rate, CH(4) production from enteric fermentation was nearly threefold less in MGP than CWP and HGP. When factors contributing to net GWP were summed, HGP and MGP were found to serve as net CO(2equiv.) sinks, while CWP was a net CO(2equiv.) source. Values for GWP and GHG intensity, however, indicated net reductions in GHG emissions can be most effectively achieved through moderate stocking rates on native vegetation in the NGP.

  15. Long term potentiation is impaired in membrane glycoprotein CD200-deficient mice: a role for Toll-like receptor activation.

    PubMed

    Costello, Derek A; Lyons, Anthony; Denieffe, Stephanie; Browne, Tara C; Cox, F Fionnuala; Lynch, Marina A

    2011-10-07

    The membrane glycoprotein CD200 is expressed on several cell types, including neurons, whereas expression of its receptor, CD200R, is restricted principally to cells of the myeloid lineage, including microglia. The interaction between CD200 and CD200R maintains microglia and macrophages in a quiescent state; therefore, CD200-deficient mice express an inflammatory phenotype exhibiting increased macrophage or microglial activation in models of arthritis, encephalitis, and uveoretinitis. Here, we report that lipopolysaccharide (LPS) and Pam(3)CysSerLys(4) exerted more profound effects on release of the proinflammatory cytokines, interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNFα), in glia prepared from CD200(-/-) mice compared with wild type mice. This effect is explained by the loss of CD200 on astrocytes, which modulates microglial activation. Expression of Toll-like receptors 4 and 2 (TLR4 and -2) was increased in glia prepared from CD200(-/-) mice, and the evidence indicates that microglial activation, assessed by the increased numbers of CD11b(+) cells that stained positively for both MHCII and CD40, was enhanced in CD200(-/-) mice compared with wild type mice. These neuroinflammatory changes were associated with impaired long term potentiation (LTP) in CA1 of hippocampal slices prepared from CD200(-/-) mice. One possible explanation for this is the increase in TNFα in hippocampal tissue prepared from CD200(-/-) mice because TNFα application inhibited LTP in CA1. Significantly, LPS and Pam(3)CysSerLys(4), at concentrations that did not affect LTP in wild type mice, inhibited LTP in slices prepared from CD200(-/-) mice, probably due to the accompanying increase in TLR2 and TLR4. Thus, the neuroinflammatory changes that result from CD200 deficiency have a negative impact on synaptic plasticity.

  16. Harmful potential toxic elements in greenhouse soils under long-term cultivation in Almería (Spain)

    NASA Astrophysics Data System (ADS)

    Joaquin Ramos-Miras, Jose; Rodríguez Martín, Jose Antonio; Boluda, Rafael; Bech, Jaume; Gil, Carlos

    2014-05-01

    Heavy metals (HM) are considered highly significant environmental contaminants and are the object of many scientific research works into the soil environment. Activities like agriculture or industry can increase the concentration of these contaminants in soils and waters, which can affect the food chain. Intensification of certain agricultural practices, constant and excessive use of fertilizers and phytosanitary products, and using machinery, increase the HM content in agricultural soils. Many studies have dealt with HM accumulation over time. Despite these works, the influence of long periods of time on these contents, the dynamics and evolution of these elements in agricultural soils, especially soils used for intensive farming purposes under greenhouse conditions, remain unknown to a certain extent. The western Almería region (Spain) is a very important area from both the socio-economic and agricultural viewpoints. A common practice in greenhouse agriculture is the addition of agrochemicals to soils and crops to improve nutrient supply or crop protection and disease control. Such intense agricultural activity has a strong impact, which may have negative repercussions on both these greenhouse soils and the environment. A research has been carried out to determine the total and available levels of six harmful potentially toxic elements (Cd, Cu, Pb, Ni, Zn and Co), and to assess long-term variations in the greenhouse soils of western Almeria. The results indicate that managing soils in the greenhouse preparation stage determines major changes in total and available HM contents. Furthermore, Cd, Cu and Pb enrichment in soil was observed depending on the element and years of growth.

  17. Impaired spatial memory and enhanced long-term potentiation in mice with forebrain-specific ablation of the Stim genes

    PubMed Central

    Garcia-Alvarez, Gisela; Shetty, Mahesh S.; Lu, Bo; Yap, Kenrick An Fu; Oh-Hora, Masatsugu; Sajikumar, Sreedharan; Bichler, Zoë; Fivaz, Marc

    2015-01-01

    Recent findings point to a central role of the endoplasmic reticulum-resident STIM (Stromal Interaction Molecule) proteins in shaping the structure and function of excitatory synapses in the mammalian brain. The impact of the Stim genes on cognitive functions remains, however, poorly understood. To explore the function of the Stim genes in learning and memory, we generated three mouse strains with conditional deletion (cKO) of Stim1 and/or Stim2 in the forebrain. Stim1, Stim2, and double Stim1/Stim2 cKO mice show no obvious brain structural defects or locomotor impairment. Analysis of spatial reference memory in the Morris water maze revealed a mild learning delay in Stim1 cKO mice, while learning and memory in Stim2 cKO mice was indistinguishable from their control littermates. Deletion of both Stim genes in the forebrain resulted, however, in a pronounced impairment in spatial learning and memory reflecting a synergistic effect of the Stim genes on the underlying neural circuits. Notably, long-term potentiation (LTP) at CA3-CA1 hippocampal synapses was markedly enhanced in Stim1/Stim2 cKO mice and was associated with increased phosphorylation of the AMPA receptor subunit GluA1, the transcriptional regulator CREB and the L-type Voltage-dependent Ca2+ channel Cav1.2 on protein kinase A (PKA) sites. We conclude that STIM1 and STIM2 are key regulators of PKA signaling and synaptic plasticity in neural circuits encoding spatial memory. Our findings also reveal an inverse correlation between LTP and spatial learning/memory and suggest that abnormal enhancement of cAMP/PKA signaling and synaptic efficacy disrupts the formation of new memories. PMID:26236206

  18. Long-Term Effects of Child Corporal Punishment on Depressive Symptoms in Young Adults: Potential Moderators and Mediators

    ERIC Educational Resources Information Center

    Turner, Heather A.; Muller, Paul A.

    2004-01-01

    Based on a sample of 649 students from 3 New England colleges, this study examined the long-term effects of childhood corporal punishment on symptoms of depression and considered factors that may moderate or mediate the association. Similar to national studies, approximately 40% of the sample reported experiencing some level of corporal punishment…

  19. Adenylyl cyclase subtype 1 is essential for late-phase long term potentiation and spatial propagation of synaptic responses in the anterior cingulate cortex of adult mice.

    PubMed

    Chen, Tao; O'Den, Gerile; Song, Qian; Koga, Kohei; Zhang, Ming-Ming; Zhuo, Min

    2014-10-10

    Long-term potentiation (LTP) is a key cellular mechanism for pathological pain in the central nervous system. LTP contains at least two different phases: early-phase LTP (E-LTP) and late-phase LTP (L-LTP). Among several major cortical areas, the anterior cingulate cortex (ACC) is a critical brain region for pain perception and its related emotional changes. Periphery tissue or nerve injuries cause LTP of excitatory synaptic transmission in the ACC. Our previous studies have demonstrated that genetic deletion of calcium-stimulated adenylyl cyclase 1 (AC1) or pharmacological application of a selective AC1 inhibitor NB001 blocked E-LTP in the ACC. However, the effect of AC1 on L-LTP, which requires new protein synthesis and is important for the process of chronic pain, has not been investigated. Here we tested the effects of NB001 on the ACC L-LTP and found that bath application of NB001 (0.1 μM) totally blocked the induction of L-LTP and recruitment of cortical circuitry without affecting basal excitatory transmission. In contrast, gabapentin, a widely used analgesic drug for neuropathic pain, did not block the induction of L-LTP and circuitry recruitment even at a high concentration (100 μM). Gabapentin non-selectively decreased basal synaptic transmission. Our results provide strong evidence that the selective AC1 inhibitor NB001 can be used to inhibit pain-related cortical L-LTP without affecting basal synaptic transmission. It also provides basic mechanisms for possible side effects of gabapentin in the central nervous system and its ineffectiveness in some patients with neuropathic pain.

  20. Effect of chloramine-T on long-term potentiation at synapses between perforant path and dentate gyrus in hippocampus of rats in vivo.

    PubMed

    Yang, Jun; Hu, Zhuang-Li; Jiang, Bo; Ni, Lan; Jin, You; Chen, Jian-Guo; Wang, Fang

    2011-03-01

    Reactive oxygen species (ROS), including superoxide, are generally considered as neurotoxic molecules whose effects can be alleviated by antioxidant enzymes. However, ROS also are known to be necessary components of the signal transduction cascades underlying normal synaptic plasticity. The oxidant chloramine-T (Ch-T), a specific oxidant to sulphur-containing residues, can oxidize methionine (Met) residues in proteins to alter protein function. To investigate the effect of Ch-T on the induction of hippocampal long-term potentiation (LTP) in dentate gyrus (DG), in vivo electrophysiological recording was employed. It was found that intracerebroventricular (ICV) injection of 0.1 μM Ch-T in 5 μL enhanced hippocampal LTP of rats slightly, whereas, 20 mM Ch-T in 5 μL greatly attenuated LTP. These effects can be reversed by pretreatment with 0.1 mM dithiothretol (DTT), a special thiol reductant. In addition, 0.1 μM Ch-T elevated LTP-induced increase in phosphorylation of Ca²+/calmodulin (CaM)-dependent protein kinase (CaMKII) and neurogranin (Ng), whereas 2 μM and 20 mM Ch-T reduced LTP-induced increase in phosphorylation status of the two key proteins, especially for 20 mM Ch-T. Pretreatment with DTT significantly prevented these effects. Taken together, these findings demonstrated that Ch-T has concentration-dependent effects on the induction of hippocampal LTP in vivo. In brief, low concentration of Ch-T facilitated hippocampal LTP by enhancing LTP-induced increase in p-CaMKII and p-Ng compared to controls, whereas high concentration of Ch-T obviously attenuated LTP accompanied by a decrease in the phosphorylated proteins, and both of these effects can be prevented by DTT. These results indicate that Ch-T modulates hippocampal LTP through regulating phosphorylation status of CaMKII and Ng.

  1. Developmental regulation of the late phase of long-term potentiation (L-LTP) and metaplasticity in hippocampal area CA1 of the rat

    PubMed Central

    Cao, Guan

    2012-01-01

    Long-term potentiation (LTP) is a form of synaptic plasticity thought to underlie memory; thus knowing its developmental profile is fundamental to understanding function. Like memory, LTP has multiple phases with distinct timing and mechanisms. The late phase of LTP (L-LTP), lasting longer than 3 h, is protein synthesis dependent and involves changes in the structure and content of dendritic spines, the major sites of excitatory synapses. In previous work, tetanic stimulation first produced L-LTP at postnatal day 15 (P15) in area CA1 of rat hippocampus. Here we used a more robust induction paradigm involving theta-burst stimulation (TBS) in acute slices and found the developmental onset of L-LTP to be 3 days earlier at P12. In contrast, at P8–11, TBS only reversed the synaptic depression that occurs from test-pulse stimulation in developing (P8–15) hippocampus. A second bout of TBS delivered 30–180 min later produced L-LTP at P10–11 but not at P8–9 and enhanced L-LTP at P12–15. Both the developmental onset and the enhanced L-LTP produced by repeated bouts of TBS were blocked by the N-methyl-d-aspartate receptor antagonist dl-2-amino-5-phosphonovaleric acid. Thus the developmental onset age is P12 for L-LTP induced by the more robust and perhaps more naturalistic TBS induction paradigm. Metaplasticity produced by repeated bouts of TBS is developmentally regulated, advancing the capacity for L-LTP from P12 to P10, but not to younger ages. Together these findings provide a new basis from which to investigate mechanisms that regulate the developmental onset of this important form of synaptic plasticity. PMID:22114158

  2. An associativity requirement for locus coeruleus-induced long-term potentiation in the dentate gyrus of the urethane-anesthetized rat.

    PubMed

    Reid, Andrew T; Harley, Carolyn W

    2010-01-01

    Norepinephrine has been hypothesized to provide a learning and memory signal. Norepinephrine long-term potentiation of perforant path input to the dentate gyrus of the hippocampus provides a model for norepinephrine initiated memory processes. However, in vitro, the pairing of perforant path stimulation and norepinephrine is not required for the occurrence of norepinephrine-dependent long-term potentiation. Since bath application of norepinephrine induces long-term changes in 2nd messenger signalling and differs in a number of ways from physiological norepinephrine release, the present study is an in vivo test of the associative requirement for the pairing of perforant path input with norepinephrine to induce long-term potentiation. Phasic activation of the locus coeruleus is provided by glutamate infusion into the locus coeruleus to initiate transient norepinephrine release in the hippocampus of urethane-anesthetized Sprague-Dawley rats. Perforant path stimulation (0.067 Hz) was given throughout the experiment in the paired condition. In the unpaired condition perforant path stimulation was interrupted 10 min prior to locus coeruleus activation and resumed 10 min after locus coeruleus activation. Locus coeruleus-induced long-term potentiation of both EPSP slope and population spike only occurred in the pairing condition. This result argues that, in vivo, temporal proximity of locus coeruleus-associated norepinephrine release and perforant path stimulation are required to induce long-term plasticity. The associativity requirement for locus coeruleus activation and perforant path stimulation in vivo is consistent with the hypothesis that norepinephrine can initiate circuit changes supporting learning and memory.

  3. Nitric Oxide Is Required for L-Type Ca2+ Channel-Dependent Long-Term Potentiation in the Hippocampus

    PubMed Central

    Pigott, Beatrice M.; Garthwaite, John

    2016-01-01

    Nitric oxide (NO) has long been implicated in the generation of long-term potentiation (LTP) and other types of synaptic plasticity, a role for which the intimate coupling between NMDA receptors (NMDARs) and the neuronal isoform of NO synthase (nNOS) is likely to be instrumental in many instances. While several types of synaptic plasticity depend on NMDARs, others do not, an example of which is LTP triggered by opening of L-type voltage-gated Ca2+ channels (L-VGCCs) in postsynaptic neurons. In CA3-CA1 synapses in the hippocampus, NMDAR-dependent LTP (LTPNMDAR) appears to be primarily expressed postsynaptically whereas L-VGCC-dependent LTP (LTPL−VGCC), which often coexists with LTPNMDAR, appears mainly to reflect enhanced presynaptic transmitter release. Since NO is an excellent candidate as a retrograde messenger mediating post-to-presynaptic signaling, we sought to determine if NO functions in LTPL−VGCC in mouse CA3-CA1 synapses. When elicited by a burst type of stimulation with NMDARs and the associated NO release blocked, LTPL−VGCC was curtailed by inhibition of NO synthase or of the NO-receptor guanylyl cyclase to the same extent as occurred with inhibition of L-VGCCs. Unlike LTPNMDAR at these synapses, LTPL−VGCC was unaffected in mice lacking endothelial NO synthase, implying that the major source of the NO is neuronal. Transient delivery of exogenous NO paired with tetanic synaptic stimulation under conditions of NMDAR blockade resulted in a long-lasting potentiation that was sensitive to inhibition of NO-receptor guanylyl cyclase but was unaffected by inhibition of L-VGCCs. The results indicate that NO, acting through its second messenger cGMP, plays an unexpectedly important role in L-VGCC-dependent, NMDAR-independent LTP, possibly as a retrograde messenger generated in response to opening of postsynaptic L-VGCCs and/or as a signal acting postsynaptically, perhaps to facilitate changes in gene expression. PMID:27445786

  4. Potential of the solid-Earth response for limiting long-term West Antarctic Ice Sheet retreat

    NASA Astrophysics Data System (ADS)

    Konrad, Hannes; Sasgen, Ingo; Pollard, David; Klemann, Volker

    2016-04-01

    for asthenosphere viscosities of 3x10^20 Pa s or higher. References Gomez, N., Pollard, D., Mitrovica, J. X., Huybers, P., & Clark, P. U. (2012). Evolution of a coupled marine ice sheet-sea level model. J. Geophys. Res. 117(F1). Konrad, H., Sasgen, I., Pollard, D. & Klemann, V. (2015). Potential of the solid-Earth response for limiting long-term West Antarctic Ice Sheet retreat in a warming climate. Earth Planet. Sci. Lett. 432, 2015.

  5. Rapid eye movement sleep deprivation decreases long-term potentiation stability and affects some glutamatergic signaling proteins during hippocampal development.

    PubMed

    Lopez, J; Roffwarg, H P; Dreher, A; Bissette, G; Karolewicz, B; Shaffery, J P

    2008-04-22

    Development of the mammalian CNS requires formation and stabilization of neuronal circuits and synaptic connections. Sensory stimulation provided by the environment orchestrates neuronal circuit formation in the waking state. Endogenous sources of activation are also implicated in these processes. Accordingly we hypothesized that sleep, especially rapid eye movement sleep (REMS), the stage characterized by high neuronal activity that is more prominent in development than adulthood, provides endogenous stimulation, which, like sensory input, helps to stabilize and refine neuronal circuits during CNS development. Young (Y: postnatal day (PN) 16) and adolescent (A: PN44) rats were rapid eye movement sleep-deprived (REMSD) by gentle cage-shaking for only 4 h on 3 consecutive days (total 12 h). The effect of REMS deprivation in Y and A rats was tested 3-7 days after the last deprivation session (Y, PN21-25; A, PN49-53) and was compared with younger (immature, I, PN9-12) untreated, age-matched, treated and normal control groups. REMS deprivation negatively affected the stability of long-term potentiation (LTP) in Y but not A animals. LTP instability in Y-REMSD animals was similar to the instability in even the more immature, untreated animals. Utilizing immunoblots, we identified changes in molecular components of glutamatergic synapses known to participate in mechanisms of synaptic refinement and plasticity. Overall, N-methyl-d-aspartate receptor subunit 2B (NR2B), N-methyl-d-aspartate receptor subunit 2A, AMPA receptor subunit 1 (GluR1), postsynaptic density protein 95 (PSD-95), and calcium/calmodulin kinase II tended to be lower in Y REMSD animals (NR2B, GluR1 and PSD-95 were significantly lower) compared with controls, an effect not present in the A animals. Taken together, these data indicate that early-life REMS deprivation reduces stability of hippocampal neuronal circuits, possibly by hindering expression of mature glutamatergic synaptic components. The findings

  6. Glacial ice composition: A potential long-term record of the chemistry of atmospheric deposition, Wind River Range, Wyoming

    SciTech Connect

    Naftz, D.L. ); Rice, J.A. ); Ranville, J.R. )

    1991-06-01

    During a reconnaissance study, ice samples were collected from Knife Point glacier to determine if glaciers in the Wind River Range Could provide a long-term record of the chemical composition of wet deposition. Eight annual ice layers comprising the years 1980-1987 were identified. The concentration of calcium, chloride, and sulfate in the annual-weighted wet deposition samples collected at the National Atmospheric deposition Program (NADP) station near Pinedale, Wyoming, showed a significant, positive correlation to the concentration of the same major ions in composite samples from the annual ice layers. results of the study imply that continuous ice cores reaching to the deeper parts of glaciers in the Wind River Range could provide long-term records of the chemical composition of wet deposition.

  7. Worldwide impact of aerosol’s time scale on the predicted long-term concentrating solar power potential

    PubMed Central

    Ruiz-Arias, Jose A.; Gueymard, Christian A.; Santos-Alamillos, Francisco J.; Pozo-Vázquez, David

    2016-01-01

    Concentrating solar technologies, which are fuelled by the direct normal component of solar irradiance (DNI), are among the most promising solar technologies. Currently, the state-of the-art methods for DNI evaluation use datasets of aerosol optical depth (AOD) with only coarse (typically monthly) temporal resolution. Using daily AOD data from both site-specific observations at ground stations as well as gridded model estimates, a methodology is developed to evaluate how the calculated long-term DNI resource is affected by using AOD data averaged over periods from 1 to 30 days. It is demonstrated here that the use of monthly representations of AOD leads to systematic underestimations of the predicted long-term DNI up to 10% in some areas with high solar resource, which may result in detrimental consequences for the bankability of concentrating solar power projects. Recommendations for the use of either daily or monthly AOD data are provided on a geographical basis. PMID:27507711

  8. Evaluating long-term annual sediment yield estimating potential of GIS interfaced MUSLE model on two micro-watersheds.

    PubMed

    Arekhi, Saleh

    2008-01-15

    Use of an event scale MUSLE model for obtaining accurate long-term annual sediment yield estimates from micro-watersheds was evaluated. Such estimates are extremely important for designing appropriate soil/water conserving measures. For easy extraction and inputting of model input parameters, the proposed model was interfaced to an Arc-View/Spatial Analyst geographic information system. Application of this GIS interfaced MUSLE model on two gauged (pine and oak forest) hilly micro-watersheds viz., Salla Rautella (0.47 km2) and Naula (0.42 km2), in Almora district of Uttaranchal, India showed that it could estimate annual sediment yields with absolute mean relative errors ranging between 12-14%. Even long-term average sediment yields for Salla Rautella (observed: 9.58 tons and estimated: 10.92 tons) and Naula: (Observed: 23.89 tons and estimated: 26.61 tons) micro-watersheds could be quite realistically simulated by the proposed model.

  9. Long-term potentiation and memory processes in the psychological works of Sigmund Freud and in the formation of neuropsychiatric symptoms.

    PubMed

    Centonze, D; Siracusano, A; Calabresi, P; Bernardi, G

    2005-01-01

    Far from disproving the model of mind functioning proposed by psychoanalysis, the recent advances in neuropsychiatrical research confirmed the crucial ideas of Sigmund Freud. The hypothesis that the origin of mental illnesses lies in the impossibility for a subject to erase the long-term effects of a remote adverse event is in tune with the view that several psychiatric disturbances reflect the activation of aberrant unconscious memory processes. Freud's insights did not stop here, but went on to describe in an extremely precise manner the neural mechanisms of memory formation almost a century before the description of long-term synaptic potentiation.

  10. Short- and long-term changes in right whale calling behavior: the potential effects of noise on acoustic communication.

    PubMed

    Parks, Susan E; Clark, C W; Tyack, P L

    2007-12-01

    The impact of anthropogenic noise on marine mammals has been an area of increasing concern over the past two decades. Most low-frequency anthropogenic noise in the ocean comes from commercial shipping which has contributed to an increase in ocean background noise over the past 150 years. The long-term impacts of these changes on marine mammals are not well understood. This paper describes both short- and long-term behavioral changes in calls produced by the endangered North Atlantic right whale (Eubalaena glacialis) and South Atlantic right whale (Eubalaena australis) in the presence of increased low-frequency noise. Right whales produce calls with a higher average fundamental frequency and they call at a lower rate in high noise conditions, possibly in response to masking from low-frequency noise. The long-term changes have occurred within the known lifespan of individual whales, indicating that a behavioral change, rather than selective pressure, has resulted in the observed differences. This study provides evidence of a behavioral change in sound production of right whales that is correlated with increased noise levels and indicates that right whales may shift call frequency to compensate for increased band-limited background noise.

  11. Emotional and Cognitive Information Processing: Relations to Behavioral Performance and Hippocampal Long-Term Potentiation In Vivo during a Spatial Water Maze Training in Rats

    ERIC Educational Resources Information Center

    Schulz, Kristina; Korz, Volker

    2010-01-01

    Emotionality as well as cognitive abilities contribute to the acquisition and retrieval of memories as well as to the consolidation of long-term potentiation (LTP), a cellular model of memory formation. However, little is known about the timescale and relative contribution of these processes. Therefore, we tested the effects of weak water maze…

  12. Assessing Potential Implications of Climate Change for Long-Term Water Resources Planning in the Colorado River Basin, Texas

    NASA Astrophysics Data System (ADS)

    Munevar, A.; Butler, S.; Anderson, R.; Rippole, J.

    2008-12-01

    exploring climate change projections and methods to assess potential impacts over the project's expected life. Following an initial qualitative risk assessment, quantitative climate scenarios were developed based on multiple coupled atmosphere-ocean general circulation model (AOGCM) simulations under a range of global emission scenarios. Projected temperature and precipitation changes were evaluated from 112 downscaled AOGCM projections. A Four scenarios were selected for detailed hydrologic evaluations using the Variable Infiltration Capacity (VIC) macroscale model. A quantile mapping procedure was applied to map future climatological period change statistics onto the long-term natural climate variability in the observed record. Simulated changes in runoff, river flow, evaporation, and evapotranspiration are used to generate adjustments to historical hydrology for assessment of potential changes to surface water availability, river water quality, riverine habitat, and Bay health. Projected temperature, precipitation, and atmospheric CO2 concentrations are used to estimate changes in agricultural demand. Sea level rise scenarios that include trends in Gulf Coast shelf subsidence are combined with changes in inflows to evaluate increased coastal erosion, upland migration of the estuary, and changes to the salinity regime. Results of the scenario-based analyses are being considered in the development of adaptive management strategies for future operations of the system and the proposed project.

  13. The extracellular matrix molecule tenascin-R and its HNK-1 carbohydrate modulate perisomatic inhibition and long-term potentiation in the CA1 region of the hippocampus.

    PubMed

    Saghatelyan, A K; Gorissen, S; Albert, M; Hertlein, B; Schachner, M; Dityatev, A

    2000-09-01

    Perisomatic inhibition of pyramidal cells regulates efferent signalling from the hippocampus. The striking presence of HNK-1, a carbohydrate expressed by neural adhesion molecules, on perisomatic interneurons and around somata of CA1 pyramidal neurons led us to apply monoclonal HNK-1 antibodies to acute murine hippocampal slices. Injection of these antibodies decreased GABAA receptor-mediated perisomatic inhibitory postsynaptic currents (pIPSCs) but did not affect dendritic IPSCs or excitatory postsynaptic currents. The decrease in the mean amplitude of evoked pIPSCs by HNK-1 antibodies was accompanied by an increase in the coefficient of variation of pIPSC amplitude, number of failures and changes in frequency but not amplitude of miniature IPSCs, suggesting that HNK-1 antibodies reduced efficacy of evoked GABA release. HNK-1 antibodies did not affect pIPSCs in knock-out mice deficient in the extracellular matrix molecule tenascin-R which carries the HNK-1 carbohydrate as analysed by immunoblotting in synaptosomal fractions prepared from the CA1 region of the hippocampus. For control, HNK-1 antibody was applied to acute sections of mice deficient in the neural cell adhesion molecule NCAM, another potential carrier of HNK-1, and resulted in decrease of pIPSCs as observed in wild-type mice. Reduction in perisomatic inhibition is expected to promote induction of long-term potentiation (LTP) by increasing the level of depolarization during theta-burst stimulation. Indeed, LTP was increased by HNK-1 antibody applied before stimulation. Moreover, LTP was reduced by an HNK-1 peptide mimic, but not control peptide. These results provide first evidence that tenascin-R and its associated HNK-1 carbohydrate modulate perisomatic inhibition and synaptic plasticity in the hippocampus.

  14. Chronic Deep Cerebellar Stimulation Promotes Long-Term Potentiation, Microstructural Plasticity, and Reorganization of Perilesional Cortical Representation in a Rodent Model

    PubMed Central

    Cooperrider, Jessica; Furmaga, Havan; Plow, Ela; Park, Hyun-Joo; Chen, Zhihong; Kidd, Grahame; Baker, Kenneth B.; Gale, John T.

    2014-01-01

    Control over postinjury CNS plasticity is a major frontier of science that, if conquered, would open new avenues for treatment of neurological disorders. Here we investigate the functional, physiological, and structural changes in the cerebral cortex associated with chronic deep brain stimulation of the cerebellar output, a treatment approach that has been shown to improve postischemia motor recovery in a rodent model of cortical infarcts. Long–Evans rats were pretrained on the pasta-matrix retrieval task, followed by induction of focal cortical ischemia and implantation of a macroelectrode in the contralesional lateral cerebellar nucleus. Animals were assigned to one of three treatment groups pseudorandomly to balance severity of poststroke motor deficits: REGULAR stimulation, BURST stimulation, or SHAM. Treatment initiated 2 weeks post surgery and continued for 5 weeks. At the end, animals were randomly selected for perilesional intracortical microstimulation mapping and tissue sampling for Western blot analysis or contributed tissue for 3D electron microscopy. Evidence of enhanced cortical plasticity with therapeutically effective stimulation is shown, marked by greater perilesional reorganization in stimulation- treated animals versus SHAM. BURST stimulation was significantly effective for promoting distal forepaw cortical representation. Stimulation-treated animals showed a twofold increase in synaptic density compared with SHAM. In addition, treated animals demonstrated increased expression of synaptic markers of long-term potentiation and plasticity, including synaptophysin, NMDAR1, CaMKII, and PSD95. These findings provide a critical foundation of how deep cerebellar stimulation may guide plastic reparative reorganization after nonprogressive brain injury and indicate strong translational potential. PMID:24990924

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

    PubMed

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

    2016-12-01

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

  16. Potentials, Limitations and Applications of long-term and mobile ad-hoc Wireless Sensor Networks for Environmental Monitoring

    NASA Astrophysics Data System (ADS)

    Bumberger, Jan; Mollenhauer, Hannes; Lapteva, Yulia; Hutschenreuther, Tino; Toepfer, Hannes; Dietrich, Peter

    2014-05-01

    To characterize environmental systems it is necessary to identify and describe processes with suitable methods. Environmental systems are often characterized by their high heterogeneity, so individual measurements for their complete representation are often not sufficient. The application of wireless sensor networks in terrestrial and aquatic ecosystems offer significant benefits as a better consideration of the local test conditions becomes possible. This can be essential for the monitoring of heterogeneous environmental systems. Significant advantages in the application of mobile ad-hoc wireless sensor networks are their self-organizing behavior, resulting in a major reduction in installation and operation costs and time. In addition, a point measurement with a sensor is significantly improved by measuring at several points. It is also possible to perform analog and digital signal processing and computation on the basis of the measured data close to the sensor. Hence, a significant reduction of the data to be transmitted can be achieved which leads to a better energy management of sensor nodes. Furthermore, their localization via satellite, the miniaturization of the nodes and long-term energy self-sufficiency are current topics under investigation. The possibilities and limitations of the applicability of wireless sensor networks for long-term and mobile environmental monitoring are presented. A concepts and realization example are given in the field of micrometeorology and soil parameters for the interaction of biotic and abiotic processes .This long term monitoring is part of the Global Change Experimental Facility (GCEF), a large field-based experimental platform to assess the effects of climate change on ecosystem functions and processes under different land-use scenarios. Furthermore a mobile ad-hoc sensor network is presented for the monitoring of water induced mass wasting processes.

  17. Role of Sialidase in Long-Term Potentiation at Mossy Fiber-CA3 Synapses and Hippocampus-Dependent Spatial Memory

    PubMed Central

    Minami, Akira; Saito, Masakazu; Mamada, Shou; Ieno, Daisuke; Hikita, Tomoya; Takahashi, Tadanobu; Otsubo, Tadamune; Ikeda, Kiyoshi; Suzuki, Takashi

    2016-01-01

    Sialic acid bound to glycans in glycolipids and glycoproteins is essential for synaptic plasticity and memory. Sialidase (EC 3.2.1.18), which has 4 isozymes including Neu1, Neu2, Neu3 and Neu4, regulates the sialylation level of glycans by removing sialic acid from sialylglycoconjugate. In the present study, we investigated the distribution of sialidase activity in rat hippocampus and the role of sialidase in hippocampal memory processing. We previously developed a highly sensitive histochemical imaging probe for sialidase activity, BTP3-Neu5Ac. BTP3-Neu5Ac was cleaved efficiently by rat Neu2 and Neu4 at pH 7.3 and by Neu1 and Neu3 at pH 4.6. When a rat hippocampal acute slice was stained with BTP3-Neu5Ac at pH 7.3, mossy fiber terminal fields showed relatively intense sialidase activity. Thus, the role of sialidase in the synaptic plasticity was investigated at mossy fiber terminal fields. The long-term potentiation (LTP) at mossy fiber-CA3 pyramidal cell synapses was impaired by 2,3-dehydro-2-deoxy-N-acetylneuraminic acid (DANA), a sialidase inhibitor. DANA also failed to decrease paired-pulse facilitation after LTP induction. We also investigated the role of sialidase in hippocampus-dependent spatial memory by using the Morris water maze. The escape latency time to reach the platform was prolonged by DANA injection into the hippocampal CA3 region or by knockdown of Neu4 without affecting motility. The results show that the regulation of sialyl signaling by Neu4 is involved in hippocampal memory processing. PMID:27783694

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

    PubMed

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

    2015-09-24

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

  19. Long-Term Consequences of Traumatic Brain Injury: Current Status of Potential Mechanisms of Injury and Neurological Outcomes

    PubMed Central

    Dietrich, W. Dalton

    2015-01-01

    Abstract Traumatic brain injury (TBI) is a significant clinical problem with few therapeutic interventions successfully translated to the clinic. Increased importance on the progressive, long-term consequences of TBI have been emphasized, both in the experimental and clinical literature. Thus, there is a need for a better understanding of the chronic consequences of TBI, with the ultimate goal of developing novel therapeutic interventions to treat the devastating consequences of brain injury. In models of mild, moderate, and severe TBI, histopathological and behavioral studies have emphasized the progressive nature of the initial traumatic insult and the involvement of multiple pathophysiological mechanisms, including sustained injury cascades leading to prolonged motor and cognitive deficits. Recently, the increased incidence in age-dependent neurodegenerative diseases in this patient population has also been emphasized. Pathomechanisms felt to be active in the acute and long-term consequences of TBI include excitotoxicity, apoptosis, inflammatory events, seizures, demyelination, white matter pathology, as well as decreased neurogenesis. The current article will review many of these pathophysiological mechanisms that may be important targets for limiting the chronic consequences of TBI. PMID:25158206

  20. Acquisition of contextual discrimination involves the appearance of a RAS-GRF1/p38 mitogen-activated protein (MAP) kinase-mediated signaling pathway that promotes long term potentiation (LTP).

    PubMed

    Jin, Shan-Xue; Arai, Junko; Tian, Xuejun; Kumar-Singh, Rajendra; Feig, Larry A

    2013-07-26

    RAS-GRF1 is a guanine nucleotide exchange factor with the ability to activate RAS and RAC GTPases in response to elevated calcium levels. We previously showed that beginning at 1 month of age, RAS-GRF1 mediates NMDA-type glutamate receptor (NMDAR)-induction of long term depression in the CA1 region of the hippocampus of mice. Here we show that beginning at 2 months of age, when mice first acquire the ability to discriminate between closely related contexts, RAS-GRF1 begins to contribute to the induction of long term potentiation (LTP) in the CA1 hippocampus by mediating the action of calcium-permeable, AMPA-type glutamate receptors (CP-AMPARs). Surprisingly, LTP induction by CP-AMPARs through RAS-GRF1 occurs via activation of p38 MAP kinase rather than ERK MAP kinase, which has more frequently been linked to LTP. Moreover, contextual discrimination is blocked by knockdown of Ras-Grf1 expression specifically in the CA1 hippocampus, infusion of a p38 MAP kinase inhibitor into the CA1 hippocampus, or the injection of an inhibitor of CP-AMPARs. These findings implicate the CA1 hippocampus in the developmentally dependent capacity to distinguish closely related contexts through the appearance of a novel LTP-supporting signaling pathway.

  1. The effect of extensive reading and paired-associate learning on long-term vocabulary retention: an event-related potential study.

    PubMed

    Chun, Eunjin; Choi, Sungmook; Kim, Junsoo

    2012-07-19

    We investigated the relative efficacy of extensive reading (ER) and paired-associate learning (PAL) in the ability of second language (L2) learners to retain new vocabulary words. To that end, we combined behavioral measures (i.e., vocabulary tests) and an event-related potential (ERP) investigation with a focus on the N400 ERP component to track short- and long-term vocabulary retention as a consequence of the two different approaches. Behavioral results indicated that both ER and PAL led to substantial short-term retention of the target words. In contrast, on a long-term basis, ER was more effective than PAL to a considerable degree as indicated by a large-size effect (d=1.35). Evidence from the N400 effects (d=1.70) observed in the parietal electrode group (P3, Pz, P4) provided further support for the superior effects of ER over PAL on long-term vocabulary retention. The converging evidence challenges the assumptions of some L2 researchers and makes a significant contribution to the literature of vocabulary acquisition, because it provides the first ERP evidence that ER is more conducive to long-term vocabulary retention than PAL.

  2. Modeling long-term changes in tundra carbon balance following wildfire, climate change, and potential nutrient addition.

    PubMed

    Jiang, Yueyang; Rastetter, Edward B; Shaver, Gaius R; Rocha, Adrian V; Zhuang, Qianlai; Kwiatkowski, Bonnie L

    2017-01-01

    To investigate the underlying mechanisms that control long-term recovery of tundra carbon (C) and nutrients after fire, we employed the Multiple Element Limitation (MEL) model to simulate 200-yr post-fire changes in the biogeochemistry of three sites along a burn severity gradient in response to increases in air temperature, CO2 concentration, nitrogen (N) deposition, and phosphorus (P) weathering rates. The simulations were conducted for severely burned, moderately burned, and unburned arctic tundra. Our simulations indicated that recovery of C balance after fire was mainly determined by the internal redistribution of nutrients among ecosystem components (controlled by air temperature), rather than the supply of nutrients from external sources (e.g., nitrogen deposition and fixation, phosphorus weathering). Increases in air temperature and atmospheric CO2 concentration resulted in (1) a net transfer of nutrient from soil organic matter to vegetation and (2) higher C : nutrient ratios in vegetation and soil organic matter. These changes led to gains in vegetation biomass C but net losses in soil organic C stocks. Under a warming climate, nutrients lost in wildfire were difficult to recover because the warming-induced acceleration in nutrient cycles caused further net nutrient loss from the system through leaching. In both burned and unburned tundra, the warming-caused acceleration in nutrient cycles and increases in ecosystem C stocks were eventually constrained by increases in soil C : nutrient ratios, which increased microbial retention of plant-available nutrients in the soil. Accelerated nutrient turnover, loss of C, and increasing soil temperatures will likely result in vegetation changes, which further regulate the long-term biogeochemical succession. Our analysis should help in the assessment of tundra C budgets and of the recovery of biogeochemical function following fire, which is in turn necessary for the maintenance of wildlife habitat and tundra

  3. Tumor induction by simian virus 40 in mice is controlled by long-term persistence of the viral genome and the immune response of the host.

    PubMed Central

    Abramczuk, J; Pan, S; Maul, G; Knowles, B B

    1984-01-01

    Simian virus 40 (SV40), which transforms mouse cells in vitro, has not been previously observed to cause tumors when injected in immunocompetent mice. We have investigated both the fate of the injected virion in mice and several immunological parameters as potential factors controlling tumorigenicity. We find that although SV40 does not replicate in mouse cells, the viral DNA can persist for many months postinjection; the majority of the viral DNA is found in the cytoplasm, but a small amount of the viral DNA is integrated at multiple sites in the host nuclear DNA. The persistence of the viral genome is independent of the ability of the mouse to mount an SV40 TSTA specific cytotoxic T-cell response and may be attributed to the cytoplasmic location of the majority of the viral genome. However, in long-term studies of SV40-injected mice, genetically identical except for the major histocompatibility complex, we find that tumors were induced in some mice of the H-2d (low cytotoxic T-lymphocyte responder to SV40 TSTA) but not of the H-2k (high responder to SV40 TSTA) haplotype. Thus, a combination of inefficient disposal of the injected virion and inefficient immunological surveillance and elimination of cells containing nuclear SV40 DNA can eventually result in SV40-induced tumors at multiple sites in mice. Images PMID:6319753

  4. Long-term potentiation in the dentate gyrus of the anaesthetized rat is accompanied by an increase in extracellular glutamate: real-time measurements using a novel dialysis electrode.

    PubMed Central

    Errington, M L; Galley, P T; Bliss, T V P

    2003-01-01

    We have used a glutamate-specific dialysis electrode to obtain real-time measurements of changes in the concentration of glutamate in the extracellular space of the hippocampus during low-frequency stimulation and following the induction of long-term potentiation (LTP). In the dentate gyrus, stimulation of the perforant path at 2 Hz for 2 min produced a transient increase in glutamate current relative to the basal value at control rates of stimulation (0.033 Hz). This activity-dependent glutamate current was significantly enhanced 35 and 90 min after the induction of LTP. The maximal 2 Hz signal was obtained during post-tetanic potentiation (PTP). There was also a more gradual increase in the basal level of extracellular glutamate following the induction of LTP. Both the basal and activity-dependent increases in glutamate current induced by tetanic stimulation were blocked by local infusion of the N-methyl-D-aspartate receptor antagonist D-APV. In areas CA1 and CA3 we were unable to detect a 2 Hz glutamate signal either before or after the induction of LTP, possibly owing to a more avid uptake of glutamate in the pyramidal cell fields. These results demonstrate that LTP in the dentate gyrus is associated with a greater concentration of extracellular glutamate following activation of potentiated synapses, either because potentiated synapses release more transmitter per impulse, or because of reduced uptake by glutamate transporters. We present arguments favouring increased release rather than decreased uptake. PMID:12740113

  5. NR2B-N-Methyl-D-Aspartate Receptors Contribute to Network Asynchrony and Loss of Long-Term Potentiation Following Mild Mechanical Injury In Vitro

    DTIC Science & Technology

    2012-08-30

    REPORT NR2B -N-METHYL-D-ASPARTATE RECEPTORS CONTRIBUTE TO NETWORK ASYNCHRONY AND LOSS OF LONG-TERM POTENTIATION FOLLOWING MILD MECHANICAL INJURY IN...integrate-and-fire model of network activity, 2) simulated an injured network, 3) predicted an important role for the NR2B -NMDA receptor in mediating...ADDRESSES U.S. Army Research Office P.O. Box 12211 Research Triangle Park, NC 27709-2211 15. SUBJECT TERMS synchrony, NR2B -NMDA receptor, network

  6. Impact of long-term treatment of onchocerciasis with ivermectin in Ecuador: potential for elimination of infection

    PubMed Central

    Vieira, Juan Carlos; Cooper, Philip J; Lovato, Raquel; Mancero, Tamara; Rivera, Jorge; Proaño, Roberto; López, Andrea A; Guderian, Ronald H; Guzmán, José Rumbea

    2007-01-01

    Background Onchocerciasis is a leading cause of blindness worldwide, hence elimination of the infection is an important health priority. Community-based treatment programs with ivermectin form the basis of control programs for the disease in Latin America. The long-term administration of ivermectin could eliminate Onchocerca volvulus infection from endemic areas in Latin America. Methods A strategy of annual to twice-annual treatments with ivermectin has been used for onchocerciasis in endemic communities in Ecuador for up to 14 years. The impact of ivermectin treatment on ocular morbidity, and O. volvulus infection and transmission was monitored in seven sentinel communities. Results Over the period 1990–2003, high rates of treatment coverage of the eligible population were maintained in endemic communities (mean 85.2% per treatment round). Ivermectin reduced the prevalence of anterior segment disease of the eye to 0% in sentinel communities and had a major impact on the prevalence and transmission of infection, with possible elimination of infection in some foci. Conclusion The distribution of ivermectin in endemic communities in Ecuador might have eliminated ocular morbidity and significant progress has been made towards elimination of the infection. A strategy of more frequent treatments with ivermectin may be required in communities where the infection persists to achieve the objective of elimination of the infection from Ecuador. The elimination of the infection from an endemic country in Latin America would be a major public health achievement and could stimulate the implementation of elimination strategies in other endemic countries. PMID:17521449

  7. Restoration of regeneration potential of long-term cultures of red fescue (Festuca rubra L.) by elevated sucrose levels.

    PubMed

    Zaghmout, O M; Torello, W A

    1992-04-01

    A tissue culture protocol for restoring embryogenic ability and increasing green plant regeneration from long-term callus (5-year old) and suspension cultures of "Dawson" red fescue (Festuca rubra var trichyoplylla Gaud) was developed. Pretreatment with elevated levels of sucrose over the standard level (60 mM) enhanced regeneration capacity and decreased the number of albino plants. The highest degree of embryogenesis and green shoot number occurred when calli were pre-treated on MS basal medium supplemented with 120 mM sucrose. Mannitol caused callus discoloration and death if added to pre-treatment media at 60, 90, 120, 150 or 180 mM. Cell suspension growth was greatest when 135 mM sucrose was added to the pre-treatment growth media. High concentrations of sucrose (135 and 180 mM) were necessary for plant regeneration from suspension aggregates pretreated with 135 or 180 mM sucrose and then plated on a growth regulator-free regeneration medium composed of half-strength MS salts and B5 vitamins.

  8. Identification of differentially expressed genes potentially involved in the tolerance of Lotus tenuis to long-term alkaline stress.

    PubMed

    Paz, Rosalía Cristina; Rocco, Rubén Anibal; Jiménez-Bremont, Juan Francisco; Rodríguez-Kessler, Margarita; Becerra-Flora, Alicia; Menéndez, Ana Bernardina; Ruíz, Oscar Adolfo

    2014-09-01

    Soil alkalinity is one of the most serious agricultural problems limiting crop yields. The legume Lotus tenuis is an important forage acknowledged by its ability to naturally grow in alkaline soils. To gain insight into the molecular responses that are activated by alkalinity in L. tenuis plants, subtractive cDNA libraries were generated from leaves and roots of these plants. Total RNAs of non-stressed plants (pH 5.8; E.C. 1.2), and plants stressed by the addition of 10 mM of NaHCO3 (pH 9.0; E.C. 1.9), were used as source of the driver and the tester samples, respectively. RNA samples were collected after 14 and 28 days of treatment. A total of 158 unigenes from leaves and 92 unigenes from roots were obtained and classified into 11 functional categories. Unigenes from these categories (4 for leaves and 8 for roots), that were related with nutrient metabolism and oxidative stress relief were selected, and their differential expression analyzed by qRT-PCR. These genes were found to be differentially expressed in a time dependent manner in L. tenuis during the alkaline stress application. Data generated from this study will contribute to the understanding of the general molecular mechanisms associated to plant tolerance under long-term alkaline stress in plants.

  9. Long-term water-quality changes in East Fork Poplar Creek, Tennessee: background, trends, and potential biological consequences.

    PubMed

    Stewart, Arthur J; Smith, John G; Loar, James M

    2011-06-01

    We review long-term changes that have occurred in factors affecting water quality in East Fork Poplar Creek (EFPC; in East Tennessee) over a nearly 25-year monitoring period. Historically, the stream has received wastewaters and pollutants from a major United States Department of Energy (DOE) facility on the headwaters of the stream. Early in the monitoring program, EFPC was perturbed chemically, especially within its headwaters; evidence of this perturbation extended downstream for many kilometers. The magnitude of this perturbation, and the concentrations of many biologically significant water-quality factors, has lessened substantially through time. The changes in water-quality factors resulted from a large number of operational changes and remedial actions implemented at the DOE facility. Chief among these were consolidation and elimination of many effluents, elimination of an unlined settling/flow equalization basin, reduction in amount of blow-down from cooling tower operations, dechlorination of effluents, and implementation of flow augmentation. Although many water-quality characteristics in upper EFPC have become more similar to those of reference streams, conditions remain far from pristine. Nutrient enrichment may be one of the more challenging problems remaining before further biological improvements occur.

  10. Endothelial Progenitor Cells of the Human Placenta and Fetoplacental Circulation: A Potential Link to Fetal, Neonatal, and Long-term Health

    PubMed Central

    Gumina, Diane L.; Su, Emily J.

    2017-01-01

    The fetoplacental circulation plays a key role in both short- and long-term outcomes, and aberrant flow indices as manifested by abnormal fetal Doppler velocimetry within this compartment have been associated with significant adverse consequences. These include fetal growth restriction, which often coexists with preeclampsia, and long-lasting medical issues as a result of both the underlying pathology and prematurity such as bronchopulmonary dysplasia, chronic lung disease, and neurodevelopmental delay. Furthermore, it is also clear that exposure to an abnormal in utero environment increases risk for long-term, adulthood issues such as cardiovascular disease. Endothelial progenitor cells (EPCs) have been implicated in vasculogenesis and angiogenesis, and they have been isolated from both human placenta and umbilical cord blood. This review outlines the extensive nomenclature of EPCs, summarizes existing literature surrounding human placental and umbilical cord blood EPCs, explores their potential role in pregnancy complications and adverse perinatal outcome, and highlights key areas where future investigations are needed. PMID:28361046

  11. Predicting ecosystem carbon balance in a warming Arctic: the importance of long-term thermal acclimation potential and inhibitory effects of light on respiration.

    PubMed

    McLaughlin, Blair C; Xu, Cheng-Yuan; Rastetter, Edward B; Griffin, Kevin L

    2014-06-01

    The carbon balance of Arctic ecosystems is particularly sensitive to global environmental change. Leaf respiration (R), a temperature-dependent key process in determining the carbon balance, is not well-understood in Arctic plants. The potential for plants to acclimate to warmer conditions could strongly impact future global carbon balance. Two key unanswered questions are (1) whether short-term temperature responses can predict long-term respiratory responses to growth in elevated temperatures and (2) to what extent the constant daylight conditions of the Arctic growing season inhibit leaf respiration. In two dominant Arctic species Eriophorum vaginatum (tussock grass) and Betula nana (woody shrub), we assessed the extent of respiratory inhibition in the light (RL/RD), respiratory response to short-term temperature change, and respiratory acclimation to long-term warming treatments. We found that R of both species is strongly inhibited by light (averaging 35% across all measurement temperatures). In E. vaginatum both RL and RD acclimated to the long-term warming treatment, reducing the magnitude of respiratory response relative to the short-term response to temperature increase. In B. nana, both RL and RD responded to short-term temperature increase but showed no acclimation to the long-term warming. The ability to predict plant respiratory response to global warming with short-term temperature responses will depend on species-specific acclimation potential and the differential response of RL and RD to temperature. With projected woody shrub encroachment in Arctic tundra and continued warming, changing species dominance between these two functional groups, may impact ecosystem respiratory response and carbon balance.

  12. Drivers, trends, and potential impacts of long-term coastal reclamation in China from 1985 to 2010

    SciTech Connect

    Tian, Bo; Wu, Wenting; Yang, Zhaoqing; Zhou, Yunxuan

    2016-03-01

    Driven by rapid economic development, population growth, and urbanization, China has experienced severe coastal land reclamation over the last decades, which resulted in significant loss of coastal wetland and wildlife habitat, and degradation of marine ecosystems. This study used advanced remote-sensing techniques to analyze the spatial and temporal distributions of coastal reclamation in China and investigated the relationships between coastal land reclamation and coastal economy, population growth, and urbanization. Analysis of long-term Landsat images time series from 1985 to 2010 in 5-year intervals, in combination with remotely sensed image techniques, indicated a sharp increasing trend of land reclamation after 2005, which accounted for over 35% of China’s total reclamation during the 25-year period since 1985. High-intensity coastal reclamation in China was mainly driven by the booming economy associated with urbanization and industrial development in the coastal region. Analysis indicated that coastal land reclamation is closely correlated with the GDP per capita in China. Study results of Landsat images showed that 754,697 ha of coastal wetlands have been reclaimed across all coastal provinces and metropolises from 1985 to 2010, at an annual rate of 5.9%. Coastal areas within the three major economic zones (Bohai Bay, Yangtze River Delta, and Pearl River Delta) were found to generally have higher reclamation rates. For example, the built-up area in Shanghai, which is located in the Yangtze River Delta, increased more than five times from 1985 to 2010. Approximately 35% of the reclamation occurred in Bohai Bay, in which the CRI between 2005 and 2010 was three times higher than the average CRI over the 25-year period.

  13. Potential role of surface wettability on the long-term stability of dentin bonds after surface biomodification.

    PubMed

    Leme, Ariene A; Vidal, Cristina M P; Hassan, Lina Saleh; Bedran-Russo, Ana K

    2015-07-16

    Degradation of the adhesive interface contributes to the failure of resin composite restorations. The hydrophilicity of the dentin matrix during and after bonding procedures may result in an adhesive interface that is more prone to degradation over time. This study assessed the effect of chemical modification of the dentin matrix on the wettability and the long-term reduced modulus of elasticity (Er) of adhesive interfaces. Human molars were divided into groups according to the priming solutions: distilled water (control), 6.5% Proanthocyanidin-rich grape seed extract (PACs), 5.75% 1-ethyl-3-[3-dimethylaminopropyl] carbodiimide hydrochloride/1.4% n-hydroxysuccinimide (EDC/NHS) and 5% Glutaraldehyde (GA). The water-surface contact angle was assessed before and after chemical modification of the dentin matrix. The demineralized dentin surface was treated with the priming solutions and restored with One Step Plus (OS) and Single Bond Plus (SB) and resin composite. Er of the adhesive, hybrid layer and underlying dentin was evaluated after 24h and 30 months in artificial saliva. The dentin hydrophilicity significantly decreased after application of the priming solutions. Aging significantly decreased Er in the hybrid layer and underlying dentin of control groups. Er of GA groups remained stable over time at the hybrid layer and underlying dentin. Significant higher Er was observed for PACs and EDC/NHS groups at the hybrid layer after 24h. The decreased hydrophilicity of the modified dentin matrix likely influence the immediate mechanical properties of the hybrid layer. Dentin biomodification prevented substantial aging at the hybrid layer and underlying dentin after 30 months storage.

  14. Burn injury during long-term oxygen therapy in Denmark and Sweden: the potential role of smoking

    PubMed Central

    Tanash, Hanan A; Ringbaek, Thomas; Huss, Fredrik; Ekström, Magnus

    2017-01-01

    Background Long-term oxygen therapy (LTOT) increases life expectancy in patients with COPD and severe hypoxemia. Smoking is the main cause of burn injury during LTOT. Policy regarding smoking while on LTOT varies between countries. In this study, we compare the incidence of burn injury that required contact with a health care specialist, between Sweden (a country with a strict policy regarding smoking while on LTOT) and Denmark (a country with less strict smoking policy). Methods This was a population-based, cohort study of patients initiating LTOT due to any cause in Sweden and Denmark. Data on diagnoses, external causes, and procedures were obtained from the Swedish and Danish National Patient Registers for inpatient and outpatient care. Patients were followed from January 1, 2000, until the first of the following: LTOT withdrawal, death, or study end (December 31, 2009). The primary end point was burn injury during LTOT. Results A total of 23,741 patients received LTOT in Denmark and 7,754 patients in Sweden. Most patients started LTOT due to COPD, both in Sweden (74%) and in Denmark (62%). The rate of burn injury while on LTOT was higher in Denmark than in Sweden; 170 (95% confidence interval [CI], 126–225) vs 85 (95% CI, 44–148) per 100,000 person-years; rate ratio 2.0 (95% CI, 1.0–4.1). The risk remained higher after adjustment for gender, age, and diagnosis in multivariate Cox regression, hazard ratio 1.8 (95% CI, 1.0−3.5). Thirty-day mortality after burn injury was 8% in both countries. Conclusion Compared to Sweden, the rate of burn injury was twice as high in Denmark where smoking is not a contraindication for prescribing LTOT. PMID:28123292

  15. Global climate change in large European rivers: long-term effects on macroinvertebrate communities and potential local confounding factors.

    PubMed

    Floury, Mathieu; Usseglio-Polatera, Philippe; Ferreol, Martial; Delattre, Cecile; Souchon, Yves

    2013-04-01

    Aquatic species living in running waters are widely acknowledged to be vulnerable to climate-induced, thermal and hydrological fluctuations. Climate changes can interact with other environmental changes to determine structural and functional attributes of communities. Although such complex interactions are most likely to occur in a multiple-stressor context as frequently encountered in large rivers, they have received little attention in such ecosystems. In this study, we aimed at specifically addressing the issue of relative long-term effects of global and local changes on benthic macroinvertebrate communities in multistressed large rivers. We assessed effects of hydroclimatic vs. water quality factors on invertebrate community structure and composition over 30 years (1979-2008) in the Middle Loire River, France. As observed in other large European rivers, water warming over the three decades (+0.9 °C between 1979-1988 and 1999-2008) and to a lesser extent discharge reduction (-80 m(3) s(-1) ) were significantly involved in the disappearance or decrease in taxa typical from fast running, cold waters (e.g. Chloroperlidae and Potamanthidae). They explained also a major part of the appearance and increase of taxa typical from slow flowing or standing waters and warmer temperatures, including invasive species (e.g. Corbicula sp. and Atyaephyra desmarestii). However, this shift towards a generalist and pollution tolerant assemblage was partially confounded by local improvement in water quality (i.e. phosphate input reduction by about two thirds and eutrophication limitation by almost one half), explaining a significant part of the settlement of new pollution-sensitive taxa (e.g. the caddisfly Brachycentridae and Philopotamidae families) during the last years of the study period. The regain in such taxa allowed maintaining a certain level of specialization in the invertebrate community despite climate change effects.

  16. Long title: Translational potential of long-term decreases in mitochondrial lipids in a mouse model of Gulf War Illness.

    PubMed

    Abdullah, Laila; Evans, James E; Joshi, Utsav; Crynen, Gogce; Reed, John; Mouzon, Benoit; Baumann, Stephan; Montague, Hannah; Zakirova, Zuchra; Emmerich, Tanja; Bachmeier, Corbin; Klimas, Nancy; Sullivan, Kimberly; Mullan, Michael; Ait-Ghezala, Ghania; Crawford, Fiona

    2016-10-29

    Gulf War Illness (GWI) affects 25% of veterans from the 1990-1991 Gulf War (GW) and is accompanied by damage to the brain regions involved in memory processing. After twenty-five years, the chronic pathobiology of GWI is still unexplained. To address this problem, we examined the long-term consequences of GW exposures in an established GWI mouse model to identify biological processes that are relevant to the chronic symptoms of GWI. Three-month old male C57BL6 mice were exposed for 10days to GW agents (pyridostigmine bromide and permethrin). Barnes Maze testing conducted at 15- and 16-months post-exposure revealed learning and memory impairment. Immunohistochemical analyses showed astroglia and microglia activation in the hippocampi of exposed mice. Proteomic studies identified perturbation of mitochondria function and metabolomics data showed decreases in the Krebs cycle compounds, lactate, β-hydroxybutyrate and glycerol-3 phosphate in the brains of exposed mice. Lipidomics data showed decreases in fatty acids, acylcarnitines and phospholipids, including cardiolipins in the brains of exposed mice. Pilot biomarker studies showed that plasma from exposed mice and veterans with GWI had increases in odd-chain, and decreases in long-chain, acylcarnitines compared to their respective controls. Very long-chain acylcarnitines were decreased in veterans with GWI compared to controls. These studies suggest that mitochondrial lipid disturbances might be associated with GWI and that further investigation is required to determine its role in the pathophysiology of this illness. Targeting mitochondrial function may provide effective therapies for GWI, and that lipid abnormalities could serve as biomarkers of GWI.

  17. Translational potential of long-term decreases in mitochondrial lipids in a mouse model of Gulf War Illness.

    PubMed

    Abdullah, Laila; Evans, James E; Joshi, Utsav; Crynen, Gogce; Reed, Jon; Mouzon, Benoit; Baumann, Stephan; Montague, Hannah; Zakirova, Zuchra; Emmerich, Tanja; Bachmeier, Corbin; Klimas, Nancy; Sullivan, Kimberly; Mullan, Michael; Ait-Ghezala, Ghania; Crawford, Fiona

    2016-11-30

    Gulf War Illness (GWI) affects 25% of veterans from the 1990-1991 Gulf War (GW) and is accompanied by damage to the brain regions involved in memory processing. After twenty-five years, the chronic pathobiology of GWI is still unexplained. To address this problem, we examined the long-term consequences of GW exposures in an established GWI mouse model to identify biological processes that are relevant to the chronic symptoms of GWI. Three-month old male C57BL6 mice were exposed for 10days to GW agents (pyridostigmine bromide and permethrin). Barnes Maze testing conducted at 15- and 16-months post-exposure revealed learning and memory impairment. Immunohistochemical analyses showed astroglia and microglia activation in the hippocampi of exposed mice. Proteomic studies identified perturbation of mitochondria function and metabolomics data showed decreases in the Krebs cycle compounds, lactate, β-hydroxybutyrate and glycerol-3 phosphate in the brains of exposed mice. Lipidomics data showed decreases in fatty acids, acylcarnitines and phospholipids, including cardiolipins in the brains of exposed mice. Pilot biomarker studies showed that plasma from exposed mice and veterans with GWI had increases in odd-chain, and decreases in long-chain, acylcarnitines compared to their respective controls. Very long-chain acylcarnitines were decreased in veterans with GWI compared to controls. These studies suggest that mitochondrial lipid disturbances might be associated with GWI and that further investigation is required to determine its role in the pathophysiology of this illness. Targeting mitochondrial function may provide effective therapies for GWI, and that lipid abnormalities could serve as biomarkers of GWI.

  18. Long-term decoding stability of local field potentials from silicon arrays in primate motor cortex during a 2D center out task

    NASA Astrophysics Data System (ADS)

    Wang, Dong; Zhang, Qiaosheng; Li, Yue; Wang, Yiwen; Zhu, Junming; Zhang, Shaomin; Zheng, Xiaoxiang

    2014-06-01

    Objective. Many serious concerns exist in the long-term stability of brain-machine interfaces (BMIs) based on spike signals (single unit activity, SUA; multi unit activity, MUA). Some studies showed local field potentials (LFPs) could offer a stable decoding performance. However, the decoding stability of LFPs was examined only when high quality spike signals were recorded. Here we aim to examine the long-term decoding stability of LFPs over a larger time scale when the quality of spike signals was from good to poor or even no spike was recorded. Approach. Neural signals were collected from motor cortex of three monkeys via silicon arrays over 230, 290 and 690 days post-implantation when they performed 2D center out task. To compare long-term stability between LFPs and spike signals, we examined them in neural signals characteristics, directional tuning properties and offline decoding performance, respectively. Main results. We observed slow decreasing trends in the number of LFP channels recorded and mean LFP power in different frequency bands when spike signals quality decayed over time. The number of significantly directional tuning LFP channels decreased more slowly than that of tuning SUA and MUA. The variable preferred directions for the same signal features across sessions indicated non-stationarity of neural activity. We also found that LFPs achieved better decoding performance than SUA and MUA in retrained decoder when the quality of spike signals seriously decayed. Especially, when no spike was recorded in one monkey after 671 days post-implantation, LFPs still provided some kinematic information. In addition, LFPs outperformed MUA in long-term decoding stability in a static decoder. Significance. Our results suggested that LFPs were more durable and could provide better decoding performance when spike signals quality seriously decayed. It might be due to their resistance to recording degradation and their high redundancy among channels.

  19. Long-Term Nutrition: A Clinician's Guide to Successful Long-Term Enteral Access in Adults.

    PubMed

    Bechtold, Matthew L; Mir, Fazia A; Boumitri, Christine; Palmer, Lena B; Evans, David C; Kiraly, Laszlo N; Nguyen, Douglas L

    2016-09-22

    Long-term nutrition support requires long-term enteral access. To ensure the success of long-term enteral access, many factors need to be taken into consideration. This article represents a guide to placing and maintaining access in patients requiring long-term nutrition and addresses many of the common questions regarding long-term enteral access, such as indications, types of access, feeding after access placed, and recognition and treatment of potential complications. This guide will help the clinician establish and maintain access to maximize nutrition in patients requiring long-term nutrition.

  20. Long-term exposure to estrogen enhances chemotherapeutic efficacy potentially through epigenetic mechanism in human breast cancer cells

    PubMed Central

    Chang, Yu-Wei

    2017-01-01

    Chemotherapy is the most common clinical option for treatment of breast cancer. However, the efficacy of chemotherapy depends on the age of breast cancer patients. Breast tissues are estrogen responsive and the levels of ovarian estrogen vary among the breast cancer patients primarily between pre- and post-menopausal age. Whether this age-dependent variation in estrogen levels influences the chemotherapeutic efficacy in breast cancer patients is not known. Therefore, the objective of this study was to evaluate the effects of natural estrogen 17 beta-estradiol (E2) on the efficacy of chemotherapeutic drugs in breast cancer cells. Estrogen responsive MCF-7 and T47D breast cancer cells were long-term exposed to 100 pg/ml estrogen, and using these cells the efficacy of chemotherapeutic drugs doxorubicin and cisplatin were determined. The result of cell viability and cell cycle analysis revealed increased sensitivities of doxorubicin and cisplatin in estrogen-exposed MCF-7 and T47D cells as compared to their respective control cells. Gene expression analysis of cell cycle, anti-apoptosis, DNA repair, and drug transporter genes further confirmed the increased efficacy of chemotherapeutic drugs in estrogen-exposed cells at molecular level. To further understand the role of epigenetic mechanism in enhanced chemotherapeutic efficacy by estrogen, cells were pre-treated with epigenetic drugs, 5-aza-2-deoxycytidine and Trichostatin A prior to doxorubicin and cisplatin treatments. The 5-aza-2 deoxycytidine pre-treatment significantly decreased the estrogen-induced efficacy of doxorubicin and cisplatin, suggesting the role of estrogen-induced hypermethylation in enhanced sensitivity of these drugs in estrogen-exposed cells. In summary, the results of this study revealed that sensitivity to chemotherapy depends on the levels of estrogen in breast cancer cells. Findings of this study will have clinical implications in selecting the chemotherapy strategies for treatment of breast

  1. Encapsulated living choroid plexus cells: potential long-term treatments for central nervous system disease and trauma

    NASA Astrophysics Data System (ADS)

    Skinner, S. J. M.; Geaney, M. S.; Lin, H.; Muzina, M.; Anal, A. K.; Elliott, R. B.; Tan, P. L. J.

    2009-12-01

    . Previously reported evidence demonstrated that CP cells support the survival and differentiation of neuronal cells in vitro and effectively treat acute brain injury and disease in rodents and non-human primates in vivo. The accumulated preclinical data together with the long-term survival of implanted encapsulated cells in vivo provide a sound base for the investigation of these treatments for chronic inherited and established neurodegenerative conditions.

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

    PubMed

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

    2016-02-01

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

  3. In vivo sodium salicylate causes tolerance to acute morphine exposure and alters the ability of high frequency stimulation to induce long-term potentiation in hippocampus area CA1.

    PubMed

    Hosseinmardi, Narges; Azimi, Lila; Fathollahi, Yaghoub; Javan, Mohammad; Naghdi, Naser

    2011-11-30

    Effects of morphine on synaptic transmission and plasticity in the hippocampus area CA1 following in vivo sodium salicylate and the potential molecular mechanism were investigated. Population spikes (PS) were recorded from stratum pylamidale of area CA1 following stimulation of Schaffer collaterals in slices taken from control and sodium salicylate injected rats. To induce long term potentiation (LTP), a 100Hz tetanic stimulation was used. Acute in vitro morphine increased baseline PS amplitude in control slices but not in slices taken from sodium salicylate treated rats. In vivo chronic salicylate did slightly decrease and/or destabilize LTP of CA1 synaptic transmission. We also found that mRNA of NR2A subunit of NMDA receptor was reduced in the hippocampus of sodium salicylate treated rats as compared to control ones. Following LTP induction, the mRNA of NR2A and PP1 (protein phosphatase 1) in slices taken from salicylate-treated rats were more than those of control ones. After long-term exposure to in vitro morphine, high frequency stimulation (HFS) decreased NR2A mRNA level significantly in sodium salicylate treated slices. It is concluded that in vivo sodium salicylate causes tolerance to excitatory effect of morphine and changes the ability of HFS to induce PS LTP in the hippocampus area CA1 in vitro. These changes in synaptic response may be due to alterations in NR2A and PP1 expression.

  4. Enhanced Long Term Potentiation and Decreased AMPA Receptor Desensitization in the Acute Period Following a Single Kainate Induced Early Life Seizure

    PubMed Central

    O'Leary, Heather; Bernard, Paul B.; Castano, Anna M.; Benke, Tim A.

    2016-01-01

    Neonatal seizures are associated with long term disabilities including epilepsy and cognitive deficits. Using a neonatal seizure rat model that does not develop epilepsy, but develops a phenotype consistent with other models of intellectual disability (ID) and autism spectrum disorders (ASD), we sought to isolate the acute effects of a single episode of early life seizure on hippocampal CA1 synaptic development and plasticity. We have previously shown chronic changes in glutamatergic synapses, loss of long term potentiation (LTP) and enhanced long term depression (LTD), in the adult male rat ~50 days following kainic acid (KA) induced early life seizure (KA-ELS) in post-natal (P) 7 day old male Sprague-Dawley rats. In the present work, we examined the electrophysiological properties and expression levels of glutamate receptors in the acute period, 2 and 7 days, post KA-ELS. Our results show for the first time enhanced LTP 7 days after KA-ELS, but no change 2 days post KA-ELS. Additionally, we report that ionotropic α-amino-3-hydroxy-5-methyl-isoxazole-propionic acid type glutamate receptor (AMPAR) desensitization is decreased in the same time frame, with no changes in AMPAR expression, phosphorylation, or membrane insertion. Inappropriate enhancement of the synaptic connections in the acute period after the seizure could alter the normal patterning of synaptic development in the hippocampus during this critical period and contribute to learning deficits. Thus, this study demonstrates a novel mechanism by which KA-ELS alters early network properties that potentially lead to adverse outcomes. PMID:26706598

  5. Protease Activated Receptor 2 (PAR2) Induces Long-Term Depression in the Hippocampus through Transient Receptor Potential Vanilloid 4 (TRPV4)

    PubMed Central

    Shavit-Stein, Efrat; Artan-Furman, Avital; Feingold, Ekaterina; Ben Shimon, Marina; Itzekson-Hayosh, Zeev; Chapman, Joab; Vlachos, Andreas; Maggio, Nicola

    2017-01-01

    Protease activated receptors (PARs) are involved in regulating synaptic transmission and plasticity in the brain. While it is well-accepted that PAR1 mediates long-term potentiation (LTP) of excitatory synaptic strength, the role of PAR2 in synaptic plasticity remains not well-understood. In this study, we assessed the role of PAR2-signaling in plasticity at hippocampal Schaffer collateral-CA1 synapses. Using field potential recordings, we report that PAR2-activation leads to long-term depression (LTD) of synaptic transmission through a protein kinase A -dependent, Transient Receptor Potential Vanilloid 4 -mediated mechanism, which requires the activation of N-methyl-D-aspartate receptors. These results demonstrate that the effects of PAR2 on synaptic plasticity are distinct from what is observed upon PAR1-activation. Thus, we propose that the activation of different classes of PARs, i.e., PAR1 and PAR2, may set the threshold of synaptic plasticity in the hippocampal network by balancing LTP and LTD. PMID:28303089

  6. Virtual Models of Long-Term Care

    ERIC Educational Resources Information Center

    Phenice, Lillian A.; Griffore, Robert J.

    2012-01-01

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

  7. Long Term Exposure to Polyphenols of Artichoke (Cynara scolymus L.) Exerts Induction of Senescence Driven Growth Arrest in the MDA-MB231 Human Breast Cancer Cell Line.

    PubMed

    Mileo, Anna Maria; Di Venere, Donato; Abbruzzese, Claudia; Miccadei, Stefania

    2015-01-01

    Polyphenolic extracts from the edible part of artichoke (Cynara scolymus L.) have been shown to be potential chemopreventive and anticancer dietary compounds. High doses of polyphenolic extracts (AEs) induce apoptosis and decrease the invasive potential of the human breast cancer cell line, MDA-MB231. However, the molecular mechanism underlying AEs antiproliferative effects is not completely understood. We demonstrate that chronic and low doses of AEs treatment at sublethal concentrations suppress human breast cancer cell growth via a caspases-independent mechanism. Furthermore, AEs exposure induces a significant increase of senescence-associated β-galactosidase (SA-β-gal) staining and upregulation of tumour suppressor genes, p16(INK4a) and p21(Cip1/Waf1) in MDA-MB231 cells. AEs treatment leads to epigenetic alterations in cancer cells, modulating DNA hypomethylation and lysine acetylation levels in total proteins. Cell growth arrest correlates with increased reactive oxygen species (ROS) production in AEs treated breast cancer cells. Inhibition of ROS generation by N-acetylcysteine (NAC) attenuates the antiproliferative effect. These findings demonstrate that chronic AEs treatment inhibits breast cancer cell growth via the induction of premature senescence through epigenetic and ROS-mediated mechanisms. Our results suggest that artichoke polyphenols could be a promising dietary tool either in cancer chemoprevention or/and in cancer treatment as a nonconventional, adjuvant therapy.

  8. Long Term Exposure to Polyphenols of Artichoke (Cynara scolymus L.) Exerts Induction of Senescence Driven Growth Arrest in the MDA-MB231 Human Breast Cancer Cell Line

    PubMed Central

    Mileo, Anna Maria; Di Venere, Donato; Abbruzzese, Claudia; Miccadei, Stefania

    2015-01-01

    Polyphenolic extracts from the edible part of artichoke (Cynara scolymus L.) have been shown to be potential chemopreventive and anticancer dietary compounds. High doses of polyphenolic extracts (AEs) induce apoptosis and decrease the invasive potential of the human breast cancer cell line, MDA-MB231. However, the molecular mechanism underlying AEs antiproliferative effects is not completely understood. We demonstrate that chronic and low doses of AEs treatment at sublethal concentrations suppress human breast cancer cell growth via a caspases-independent mechanism. Furthermore, AEs exposure induces a significant increase of senescence-associated β-galactosidase (SA-β-gal) staining and upregulation of tumour suppressor genes, p16INK4a and p21Cip1/Waf1 in MDA-MB231 cells. AEs treatment leads to epigenetic alterations in cancer cells, modulating DNA hypomethylation and lysine acetylation levels in total proteins. Cell growth arrest correlates with increased reactive oxygen species (ROS) production in AEs treated breast cancer cells. Inhibition of ROS generation by N-acetylcysteine (NAC) attenuates the antiproliferative effect. These findings demonstrate that chronic AEs treatment inhibits breast cancer cell growth via the induction of premature senescence through epigenetic and ROS-mediated mechanisms. Our results suggest that artichoke polyphenols could be a promising dietary tool either in cancer chemoprevention or/and in cancer treatment as a nonconventional, adjuvant therapy. PMID:26180585

  9. The 5-HT(7) receptor antagonist SB 269970 counteracts restraint stress-induced attenuation of long-term potentiation in rat frontal cortex.

    PubMed

    Tokarski, K; Bobula, B; Kusek, M; Hess, G

    2011-12-01

    The effects of restraint lasting for 10 min, repeated twice daily for 3 days, were studied ex vivo in rat frontal cortex slices prepared 24 h after the last stress session. In slices originating from stressed animals, the amplitude of extracellular field potentials recorded in cortical layer II/III was increased. Stress also resulted in a reduced magnitude of long-term potentiation (LTP) of field potentials. In a separate experimental group, rats were subjected to restraint lasting for 10 min, twice daily for 3 days but, additionally, animals received injections of 5-HT(7) receptor antagonist SB 269970 (1.25 mg/kg) before each restraint stress session. In this group, the amplitude of field potentials and the magnitude of LTP were not different from the control, indicating that stress-induced modifications of basal glutamatergic transmission and synaptic plasticity were prevented by the 5-HT(7) receptor antagonist.

  10. Long-term no-till and stover retention each decrease the global warming potential of irrigated continuous corn

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Over twenty-two million hectares of U.S. croplands are irrigated, but the impacts of continuous crop residue removal and tillage on soil organic carbon (SOC) stocks, soil greenhouse gas (GHG) emissions, and global warming potential (GWP) in irrigated cropping systems are relatively unknown. Residue...

  11. The coumarin scopoletin potentiates acetylcholine release from synaptosomes, amplifies hippocampal long-term potentiation and ameliorates anticholinergic- and age-impaired memory

    PubMed Central

    Hornick, A.; Lieb, A.; Vo, N.P.; Rollinger, J.M.; Stuppner, H.; Prast, H.

    2011-01-01

    In a previous study the simple, naturally derived coumarin scopoletin (SCT) was identified as an inhibitor of acetylcholinesterase (AChE), using a pharmacophore-based virtual screening approach. In this study the potential of SCT as procholinergic and cognition-enhancing therapeutic was investigated in a more detailed way, using different experimental approaches like measuring newly synthesized acetylcholine (ACh) in synaptosomes, long-term potentiation (LTP) experiments in hippocampal slices, and behavior studies. SCT enhanced the K+-stimulated release of ACh from rat frontal cortex synaptosomes, showing a bell-shaped dose effect curve (Emax: 4 μM). This effect was blocked by the nicotinic ACh receptor (nAChR) antagonists mecamylamine (MEC) and dihydro-β-erythroidine (DHE). The nAChR agonist (and AChE inhibitor) galantamine induced a similar increase in ACh release (Emax: 1 μM). SCT potentiated LTP in hippocampal slices of rat brain. The high-frequency stimulation (HFS)-induced, N-methyl-D-aspartate (NMDA) receptor dependent LTP of field excitatory postsynaptic potentials at CA3-CA1 synapses was greatly enhanced by pre-HFS application of SCT (4 μM for 4 min). This effect was mimicked by nicotine (2 μM) and abolished by MEC, suggesting an effect on nAChRs. SCT did not restore the total inhibition of LTP by NMDA receptor antagonist d, l-2-amino-5-phosphonopentanoic acid (AP-5). SCT (2 μg, i.c.v.) increased T-maze alternation and ameliorated novel object recognition of mice with scopolamine-induced cholinergic deficit. It also reduced age-associated deficits in object memory of 15–18-month-old mice (2 mg/kg sc). Our findings suggest that SCT possesses memory-improving properties, which are based on its direct nAChR agonistic activity. Therefore, SCT might be able to rescue impaired cholinergic functions by enhancing nAChR-mediated release of neurotransmitters and promoting neural plasticity in hippocampus. PMID:21945033

  12. The Role of Protein Synthesis and Monoamines in the Production of Long-Term Potentiation in the Rat Hippocampal Slice

    DTIC Science & Technology

    1985-04-01

    slices. Dingledine, R. ed., Plenum Press, N~Y. pp.145-147. Haas, H.L. and Konnerth, A. (1983) Histamine and noradrenaline decrease calcium-activated...that ~1- receptor stimulation of adenylate cyclase is probably the mechanism of NE’s action in the production of LTP in the dentate. These results...pharmacologic data support the conclusion that both phases of NE-induced potentiation are produced by e1- receptor stimulation of adenylate cyclase. This

  13. Long-Term Fructose Intake Increases Adipogenic Potential: Evidence of Direct Effects of Fructose on Adipocyte Precursor Cells.

    PubMed

    Zubiría, María Guillermina; Alzamendi, Ana; Moreno, Griselda; Rey, María Amanda; Spinedi, Eduardo; Giovambattista, Andrés

    2016-04-02

    We have previously addressed that fructose rich diet (FRD) intake for three weeks increases the adipogenic potential of stromal vascular fraction cells from the retroperitoneal adipose tissue (RPAT). We have now evaluated the effect of prolonged FRD intake (eight weeks) on metabolic parameters, number of adipocyte precursor cells (APCs) and in vitro adipogenic potential from control (CTR) and FRD adult male rats. Additionally, we have examined the direct fructose effects on the adipogenic capacity of normal APCs. FRD fed rats had increased plasma levels of insulin, triglyceride and leptin, and RPAT mass and adipocyte size. FACS studies showed higher APCs number and adipogenic potential in FRD RPAT pads; data is supported by high mRNA levels of competency markers: PPARγ2 and Zfp423. Complementary in vitro experiments indicate that fructose-exposed normal APCs displayed an overall increased adipogenic capacity. We conclude that the RPAT mass expansion observed in eight week-FRD fed rats depends on combined accelerated adipogenesis and adipocyte hypertrophy, partially due to a direct effect of fructose on APCs.

  14. Long-Term Fructose Intake Increases Adipogenic Potential: Evidence of Direct Effects of Fructose on Adipocyte Precursor Cells

    PubMed Central

    Zubiría, María Guillermina; Alzamendi, Ana; Moreno, Griselda; Rey, María Amanda; Spinedi, Eduardo; Giovambattista, Andrés

    2016-01-01

    We have previously addressed that fructose rich diet (FRD) intake for three weeks increases the adipogenic potential of stromal vascular fraction cells from the retroperitoneal adipose tissue (RPAT). We have now evaluated the effect of prolonged FRD intake (eight weeks) on metabolic parameters, number of adipocyte precursor cells (APCs) and in vitro adipogenic potential from control (CTR) and FRD adult male rats. Additionally, we have examined the direct fructose effects on the adipogenic capacity of normal APCs. FRD fed rats had increased plasma levels of insulin, triglyceride and leptin, and RPAT mass and adipocyte size. FACS studies showed higher APCs number and adipogenic potential in FRD RPAT pads; data is supported by high mRNA levels of competency markers: PPARγ2 and Zfp423. Complementary in vitro experiments indicate that fructose-exposed normal APCs displayed an overall increased adipogenic capacity. We conclude that the RPAT mass expansion observed in eight week-FRD fed rats depends on combined accelerated adipogenesis and adipocyte hypertrophy, partially due to a direct effect of fructose on APCs. PMID:27049396

  15. FOXC1 maintains the hair follicle stem cell niche and governs stem cell quiescence to preserve long-term tissue-regenerating potential.

    PubMed

    Lay, Kenneth; Kume, Tsutomu; Fuchs, Elaine

    2016-03-15

    Adult tissue stem cells (SCs) reside in niches, which orchestrate SC behavior. SCs are typically used sparingly and exist in quiescence unless activated for tissue growth. Whether parsimonious SC use is essential to conserve long-term tissue-regenerating potential during normal homeostasis remains poorly understood. Here, we examine this issue by conditionally ablating a key transcription factor Forkhead box C1 (FOXC1) expressed in hair follicle SCs (HFSCs). FOXC1-deficient HFSCs spend less time in quiescence, leading to markedly shortened resting periods between hair cycles. The enhanced hair cycling accelerates HFSC expenditure, and impacts hair regeneration in aging mice. Interestingly, although FOXC1-deficient HFs can still form a new bulge that houses HFSCs for the next hair cycle, the older bulge is left unanchored. As the new hair emerges, the entire old bulge, including its reserve HFSCs and SC-inhibitory inner cell layer, is lost. We trace this mechanism first, to a marked increase in cell cycle-associated transcripts upon Foxc1 ablation, and second, to a downstream reduction in E-cadherin-mediated inter-SC adhesion. Finally, we show that when the old bulge is lost with each hair cycle, overall levels of SC-inhibitory factors are reduced, further lowering the threshold for HFSC activity. Taken together, our findings suggest that HFSCs have restricted potential in vivo, which they conserve by coupling quiescence to adhesion-mediated niche maintenance, thereby achieving long-term tissue homeostasis.

  16. Acutely applied MDMA enhances long-term potentiation in rat hippocampus involving D1/D5 and 5-HT2 receptors through a polysynaptic mechanism.

    PubMed

    Rozas, C; Loyola, S; Ugarte, G; Zeise, M L; Reyes-Parada, M; Pancetti, F; Rojas, P; Morales, B

    2012-08-01

    3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is a drug of abuse that induces learning and memory deficit. However, there are no experimental data that correlate the behavioral evidence with models of synaptic plasticity such as long-term potentiation (LTP) or long-term depression (LTD). Using field potential recordings in rat hippocampal slices of young rats, we found that acute application of MDMA enhances LTP in CA3-CA1 synapses without affecting LTD. Using specific antagonists and paired-pulse facilitation protocols we observed that the MDMA-dependent increase of LTP involves presynaptic 5-HT₂ serotonin receptors and postsynaptic D1/D5 dopamine receptors. In addition, the inhibition of PKA suppresses the MDMA-dependent increase in LTP, suggesting that dopamine receptor agonism activates cAMP-dependent intracellular pathways. We propose that MDMA exerts its LTP-altering effect involving a polysynaptic interaction between serotonergic and dopaminergic systems in hippocampal synapses. Our results are compatible with the view that the alterations in hippocampal LTP could be responsible for MDMA-dependent cognitive deficits observed in humans and animals.

  17. FOXC1 maintains the hair follicle stem cell niche and governs stem cell quiescence to preserve long-term tissue-regenerating potential

    PubMed Central

    Lay, Kenneth; Kume, Tsutomu; Fuchs, Elaine

    2016-01-01

    Adult tissue stem cells (SCs) reside in niches, which orchestrate SC behavior. SCs are typically used sparingly and exist in quiescence unless activated for tissue growth. Whether parsimonious SC use is essential to conserve long-term tissue-regenerating potential during normal homeostasis remains poorly understood. Here, we examine this issue by conditionally ablating a key transcription factor Forkhead box C1 (FOXC1) expressed in hair follicle SCs (HFSCs). FOXC1-deficient HFSCs spend less time in quiescence, leading to markedly shortened resting periods between hair cycles. The enhanced hair cycling accelerates HFSC expenditure, and impacts hair regeneration in aging mice. Interestingly, although FOXC1-deficient HFs can still form a new bulge that houses HFSCs for the next hair cycle, the older bulge is left unanchored. As the new hair emerges, the entire old bulge, including its reserve HFSCs and SC-inhibitory inner cell layer, is lost. We trace this mechanism first, to a marked increase in cell cycle-associated transcripts upon Foxc1 ablation, and second, to a downstream reduction in E-cadherin–mediated inter-SC adhesion. Finally, we show that when the old bulge is lost with each hair cycle, overall levels of SC-inhibitory factors are reduced, further lowering the threshold for HFSC activity. Taken together, our findings suggest that HFSCs have restricted potential in vivo, which they conserve by coupling quiescence to adhesion-mediated niche maintenance, thereby achieving long-term tissue homeostasis. PMID:26912458

  18. Long Term Sugarcane Crop Residue Retention Offers Limited Potential to Reduce Nitrogen Fertilizer Rates in Australian Wet Tropical Environments

    PubMed Central

    Meier, Elizabeth A.; Thorburn, Peter J.

    2016-01-01

    The warming of world climate systems is driving interest in the mitigation of greenhouse gas (GHG) emissions. In the agricultural sector, practices that mitigate GHG emissions include those that (1) reduce emissions [e.g., those that reduce nitrous oxide (N2O) emissions by avoiding excess nitrogen (N) fertilizer application], and (2) increase soil organic carbon (SOC) stocks (e.g., by retaining instead of burning crop residues). Sugarcane is a globally important crop that can have substantial inputs of N fertilizer and which produces large amounts of crop residues (‘trash’). Management of N fertilizer and trash affects soil carbon and nitrogen cycling, and hence GHG emissions. Trash has historically been burned at harvest, but increasingly is being retained on the soil surface as a ‘trash blanket’ in many countries. The potential for trash retention to alter N fertilizer requirements and sequester SOC was investigated in this study. The APSIM model was calibrated with data from field and laboratory studies of trash decomposition in the wet tropics of northern Australia. APSIM was then validated against four independent data sets, before simulating location × soil × fertilizer × trash management scenarios. Soil carbon increased in trash blanketed soils relative to SOC in soils with burnt trash. However, further increases in SOC for the study region may be limited because the SOC in trash blanketed soils could be approaching equilibrium; future GHG mitigation efforts in this region should therefore focus on N fertilizer management. Simulated N fertilizer rates were able to be reduced from conventional rates regardless of trash management, because of low yield potential in the wet tropics. For crops subjected to continuous trash blanketing, there was substantial immobilization of N in decomposing trash so conventional N fertilizer rates were required for up to 24 years after trash blanketing commenced. After this period, there was potential to reduce N

  19. Premature loss of primary anterior teeth due to trauma--potential short- and long-term sequelae.

    PubMed

    Holan, Gideon; Needleman, Howard L

    2014-04-01

    Traumatic dental injuries (TDIs) can result in the premature loss of primary anterior teeth due to an immediate avulsion, extraction later after the injury because of poor prognosis or late complications, or early exfoliation. There are a number of potential considerations or sequelae as a result of this premature loss that have been cited in the dental literature, which include esthetics, quality of life, eating, speech development, arch integrity (space loss), development and eruption of the permanent successors, and development of oral habits. This article provides a comprehensive review of the dental literature on the possible consequences of premature loss of maxillary primary incisors following TDI.

  20. Effectivity of a strategy in elderly AML patients to reach allogeneic stem cell transplantation using intensive chemotherapy: Long-term survival is dependent on complete remission after first induction therapy.

    PubMed

    von dem Borne, P A; de Wreede, L C; Halkes, C J M; Marijt, W A F; Falkenburg, J H F; Veelken, H

    2016-07-01

    Intensive chemotherapy followed by allogeneic stem cell transplantation (alloSCT) can cure AML. Most studies on alloSCT in elderly AML report results of highly selected patient cohorts. Hardly any data exist on the effectiveness of prospective strategies intended to bring as many patients as possible to transplant. Between 2006 and 2011 we implemented a treatment algorithm for all newly diagnosed AML patients aged 61-75 years, consisting of intensive chemotherapy cycles to induce complete remission, followed by alloSCT. 44 of 60 (73%) newly diagnosed elderly AML patients started with chemotherapy. By meticulously following our algorithm in almost all patients, we could induce complete remission (CR) in 66% of patients starting with chemotherapy, and transplant 32% of these patients in continuous CR. Main reasons for failure were early relapse (16%), early death (14%), primary refractory disease (9%), and patient or physician decision to stop treatment (16%). Patients in continuous CR after first induction benefit most with 36% long-term survival. Patients not in CR after first induction benefit less; although additional chemotherapy induces CR in 45% of these patients, only 23% are transplanted and no long-term survival is observed, mainly due to relapse. Long-term survival in the group of 44 patients is 9% (median 4.5 years after alloSCT). Considering that 27% of patients do not start with chemotherapy and 64% of patients starting with chemotherapy do not reach alloSCT, the reasons for failure presented here should be used as a guide to develop new treatment algorithms to improve long-term survival in elderly AML patients.

  1. A greener Greenland? Climatic potential and long-term constraints on future expansions of trees and shrubs.

    PubMed

    Normand, Signe; Randin, Christophe; Ohlemüller, Ralf; Bay, Christian; Høye, Toke T; Kjær, Erik D; Körner, Christian; Lischke, Heike; Maiorano, Luigi; Paulsen, Jens; Pearman, Peter B; Psomas, Achilleas; Treier, Urs A; Zimmermann, Niklaus E; Svenning, Jens-Christian

    2013-08-19

    Warming-induced expansion of trees and shrubs into tundra vegetation will strongly impact Arctic ecosystems. Today, a small subset of the boreal woody flora found during certain Plio-Pleistocene warm periods inhabits Greenland. Whether the twenty-first century warming will induce a re-colonization of a rich woody flora depends on the roles of climate and migration limitations in shaping species ranges. Using potential treeline and climatic niche modelling, we project shifts in areas climatically suitable for tree growth and 56 Greenlandic, North American and European tree and shrub species from the Last Glacial Maximum through the present and into the future. In combination with observed tree plantings, our modelling highlights that a majority of the non-native species find climatically suitable conditions in certain parts of Greenland today, even in areas harbouring no native trees. Analyses of analogous climates indicate that these conditions are widespread outside Greenland, thus increasing the likelihood of woody invasions. Nonetheless, we find a substantial migration lag for Greenland's current and future woody flora. In conclusion, the projected climatic scope for future expansions is strongly limited by dispersal, soil development and other disequilibrium dynamics, with plantings and unintentional seed dispersal by humans having potentially large impacts on spread rates.

  2. A greener Greenland? Climatic potential and long-term constraints on future expansions of trees and shrubs

    PubMed Central

    Normand, Signe; Randin, Christophe; Ohlemüller, Ralf; Bay, Christian; Høye, Toke T.; Kjær, Erik D.; Körner, Christian; Lischke, Heike; Maiorano, Luigi; Paulsen, Jens; Pearman, Peter B.; Psomas, Achilleas; Treier, Urs A.; Zimmermann, Niklaus E.; Svenning, Jens-Christian

    2013-01-01

    Warming-induced expansion of trees and shrubs into tundra vegetation will strongly impact Arctic ecosystems. Today, a small subset of the boreal woody flora found during certain Plio-Pleistocene warm periods inhabits Greenland. Whether the twenty-first century warming will induce a re-colonization of a rich woody flora depends on the roles of climate and migration limitations in shaping species ranges. Using potential treeline and climatic niche modelling, we project shifts in areas climatically suitable for tree growth and 56 Greenlandic, North American and European tree and shrub species from the Last Glacial Maximum through the present and into the future. In combination with observed tree plantings, our modelling highlights that a majority of the non-native species find climatically suitable conditions in certain parts of Greenland today, even in areas harbouring no native trees. Analyses of analogous climates indicate that these conditions are widespread outside Greenland, thus increasing the likelihood of woody invasions. Nonetheless, we find a substantial migration lag for Greenland's current and future woody flora. In conclusion, the projected climatic scope for future expansions is strongly limited by dispersal, soil development and other disequilibrium dynamics, with plantings and unintentional seed dispersal by humans having potentially large impacts on spread rates. PMID:23836785

  3. Long-term use of biosolids as organic fertilizers in agricultural soils: potentially toxic elements occurrence and mobility.

    PubMed

    Marguí, E; Iglesias, M; Camps, F; Sala, L; Hidalgo, M

    2016-03-01

    The presence of potentially toxic elements (PTEs) may hinder a more widespread application of biosolids in agriculture. At present, the European Directive 86/278/CEE limit the total concentrations of seven metals (Cu, Cr, Ni, Pb, Zn, Cd and Hg) in agricultural soils and in sewage sludges used as fertilizers but it has not taken into consideration the potential impacts of other emerging micropollutants that may be present in the biosolids as well as their mobility. The aim of this study was to evaluate the accumulation and mobility of 13 elements (including regulated metals and other inorganic species) in agricultural soils repeatedly amended with biosolids for 15 years. Firstly, three digestions programs using different acid mixtures were tested to evaluate the most accurate and efficient method for analysis of soil and sludge. Results demonstrated that sewage sludge application increased concentrations of Pb and Hg in soil, but values did not exceed the quality standard established by legislation. In addition, other elements (As, Co, Sb, Ag, Se and Mn) that at present are not regulated by the Spanish and European directives were identified in the sewage sludge, and significant differences were found between Ag content in soils amended with biosolids in comparison with control soils. This fact can be related to the increasing use of silver nanoparticles in consumer products due to their antibacterial properties. Results from the leaching tests show up that, in general, the mobility degree for both regulated and non-regulated elements in soils amended with biosolids was quite low (<10 %).

  4. Induction of long-term oscillations in the γ frequency band by nAChR activation in rat hippocampal CA3 area.

    PubMed

    Zhang, X; Ge, X Y; Wang, J G; Wang, Y L; Wang, Y; Yu, Y; Li, P P; Lu, C B

    2015-08-20

    The hippocampal neuronal network oscillation at γ frequency band (γ oscillation) is generated by the precise interaction between interneurons and principle cells. γ oscillation is associated with attention, learning and memory and is impaired in the diseased conditions such as Alzheimer's disease (AD) and schizophrenia. Nicotinic acetylcholine receptor (nAChR) plays an important role in the regulation of hippocampal neurotransmission and network activity. It is not known whether nicotine modulates plasticity of network activity at γ oscillations in the hippocampus. In this study we investigated the effects of nicotine on the long-term changes of KA-induced γ oscillations. We found that hippocampal γ oscillations can be enhanced by a low concentration of nicotine (1μM), such an enhancement lasts for hours after washing out of nicotine, suggesting a form of synaptic plasticity, named as long-term oscillation at γ frequency band (LTOγ). Nicotine-induced LTOγ was mimicked by the selective α4β2 but not by α7 nAChR agonist and was involved in N-methyl-d-aspartate (NMDA) receptor activation as well as depended on excitatory and inhibitory neurotransmission. Our results indicate that nAChR activation induced plasticity in γ oscillation, which may be beneficial for the improvement of cognitive deficiency in AD and schizophrenia.

  5. Predicting the effects of human developments on individual dolphins to understand potential long-term population consequences.

    PubMed

    Pirotta, Enrico; Harwood, John; Thompson, Paul M; New, Leslie; Cheney, Barbara; Arso, Monica; Hammond, Philip S; Donovan, Carl; Lusseau, David

    2015-11-07

    Human activities that impact wildlife do not necessarily remove individuals from populations. They may also change individual behaviour in ways that have sublethal effects. This has driven interest in developing analytical tools that predict the population consequences of short-term behavioural responses. In this study, we incorporate empirical information on the ecology of a population of bottlenose dolphins into an individual-based model that predicts how individuals' behavioural dynamics arise from their underlying motivational states, as well as their interaction with boat traffic and dredging activities. We simulate the potential effects of proposed coastal developments on this population and predict that the operational phase may affect animals' motivational states. For such results to be relevant for management, the effects on individuals' vital rates also need to be quantified. We investigate whether the relationship between an individual's exposure and the survival of its calves can be directly estimated using a Bayesian multi-stage model for calf survival. The results suggest that any effect on calf survival is probably small and that a significant relationship could only be detected in large, closely studied populations. Our work can be used to guide management decisions, accelerate the consenting process for coastal and offshore developments and design targeted monitoring.

  6. Predicting the effects of human developments on individual dolphins to understand potential long-term population consequences

    PubMed Central

    Pirotta, Enrico; Harwood, John; Thompson, Paul M.; New, Leslie; Cheney, Barbara; Arso, Monica; Hammond, Philip S.; Donovan, Carl; Lusseau, David

    2015-01-01

    Human activities that impact wildlife do not necessarily remove individuals from populations. They may also change individual behaviour in ways that have sublethal effects. This has driven interest in developing analytical tools that predict the population consequences of short-term behavioural responses. In this study, we incorporate empirical information on the ecology of a population of bottlenose dolphins into an individual-based model that predicts how individuals' behavioural dynamics arise from their underlying motivational states, as well as their interaction with boat traffic and dredging activities. We simulate the potential effects of proposed coastal developments on this population and predict that the operational phase may affect animals' motivational states. For such results to be relevant for management, the effects on individuals' vital rates also need to be quantified. We investigate whether the relationship between an individual's exposure and the survival of its calves can be directly estimated using a Bayesian multi-stage model for calf survival. The results suggest that any effect on calf survival is probably small and that a significant relationship could only be detected in large, closely studied populations. Our work can be used to guide management decisions, accelerate the consenting process for coastal and offshore developments and design targeted monitoring. PMID:26511044

  7. High dispersal potential has maintained long-term population stability in the North Atlantic copepod Calanus finmarchicus

    PubMed Central

    Provan, Jim; Beatty, Gemma E.; Keating, Sianan L.; Maggs, Christine A.; Savidge, Graham

    2008-01-01

    The cool-water copepod Calanus finmarchicus is a key species in North Atlantic marine ecosystems since it represents an important food resource for the developmental stages of several fish of major economic value. Over the last 40 years, however, data from the Continuous Plankton Recorder survey have highlighted a 70 per cent reduction in C. finmarchicus biomass, coupled with a gradual northward shift in the species's distribution, which have both been linked with climate change. To determine the potential for C. finmarchicus to track changes in habitat availability and maintain stable effective population sizes, we have assessed levels of gene flow and dispersal in current populations, as well as using a coalescent approach together with palaeodistribution modelling to elucidate the historical population demography of the species over previous changes in Earth's climate. Our findings indicate high levels of dispersal and a constant effective population size over the period 359 000–566 000 BP and suggest that C. finmarchicus possesses the capacity to track changes in available habitat, a feature that may be of crucial importance to the species's ability to cope with the current period of global climate change. PMID:18812293

  8. Long-term implications of sustained wind power growth in the United States: Potential benefits and secondary impacts

    SciTech Connect

    Wiser, Ryan; Bolinger, Mark; Heath, Garvin; Keyser, David; Lantz, Eric; Macknick, Jordan; Mai, Trieu; Millstein, Dev

    2016-10-01

    We model scenarios of the U.S. electric sector in which wind generation reaches 10% of end-use electricity demand in 2020, 20% in 2030, and 35% in 2050. As shown in a companion paper, achieving these penetration levels would have significant implications for the wind industry and the broader electric sector. Compared to a baseline that assumes no new wind deployment, under the primary scenario modeled, achieving these penetrations imposes an incremental cost to electricity consumers of less than 1% through 2030. These cost implications, however, should be balanced against the variety of environmental and social implications of such a scenario. Relative to a baseline that assumes no new wind deployment, our analysis shows that the high-penetration wind scenario yields potential greenhouse-gas benefits of $85-$1,230 billion in present-value terms, with a central estimate of $400 billion. Air-pollution-related health benefits are estimated at $52-$272 billion, while annual electric-sector water withdrawals and consumption are lower by 15% and 23% in 2050, respectively. We also find that a high-wind-energy future would have implications for the diversity and risk of energy supply, local economic development, and land use and related local impacts on communities and ecosystems; however, these additional impacts may not greatly affect aggregate social welfare owing to their nature, in part, as resource transfers.

  9. Long-Term Task- and Dopamine-Dependent Dynamics of Subthalamic Local Field Potentials in Parkinson’s Disease

    PubMed Central

    Hanrahan, Sara J.; Nedrud, Joshua J.; Davidson, Bradley S.; Farris, Sierra; Giroux, Monique; Haug, Aaron; Mahoor, Mohammad H.; Silverman, Anne K.; Zhang, Jun Jason; Hebb, Adam Olding

    2016-01-01

    Subthalamic nucleus (STN) local field potentials (LFP) are neural signals that have been shown to reveal motor and language behavior, as well as pathological parkinsonian states. We use a research-grade implantable neurostimulator (INS) with data collection capabilities to record STN-LFP outside the operating room to determine the reliability of the signals over time and assess their dynamics with respect to behavior and dopaminergic medication. Seven subjects were implanted with the recording augmented deep brain stimulation (DBS) system, and bilateral STN-LFP recordings were collected in the clinic over twelve months. Subjects were cued to perform voluntary motor and language behaviors in on and off medication states. The STN-LFP recorded with the INS demonstrated behavior-modulated desynchronization of beta frequency (13–30 Hz) and synchronization of low gamma frequency (35–70 Hz) oscillations. Dopaminergic medication did not diminish the relative beta frequency oscillatory desynchronization with movement. However, movement-related gamma frequency oscillatory synchronization was only observed in the medication on state. We observed significant inter-subject variability, but observed consistent STN-LFP activity across recording systems and over a one-year period for each subject. These findings demonstrate that an INS system can provide robust STN-LFP recordings in ambulatory patients, allowing for these signals to be recorded in settings that better represent natural environments in which patients are in a variety of medication states. PMID:27916831

  10. Preliminary Assessment of Potential Habitat Composites' Durability when Exposed to a Long-Term Radiation Environment and Micrometeoroid Impacts

    NASA Technical Reports Server (NTRS)

    Rojdev, Kristina; Graves, Russell; Golden, John; Atwell, William; O'Rouke, Mary Jane; Hill, Charles; Alred, John

    2011-01-01

    NASA's exploration goals include extending human presence beyond low earth orbit (LEO). As a result, habitation for crew is a critical requirement for meeting this goal. However, habitats are very large structures that contain a multitude of subsystems to sustain human life over long-durations in space, and one of the key challenges has been keeping weight to a minimum in order to reduce costs. Thus, light-weight and multifunctional structural materials are of great interest for habitation. NASA has started studying polymeric composite materials as potential lightweight and multifunctional structural materials for use in long-duration spaceflight. However, little is known about the survivability of these materials when exposed to the space environment outside of LEO for long durations. Thus, a study has been undertaken to investigate the durability of composite materials when exposed to long-duration radiation. Furthermore, as an addition to the primary study, a secondary preliminary investigation has been started on the micrometeoroid and orbital debris (MMOD) susceptibility of these materials after radiation exposure. The combined effects of radiation and MMOD impacts are the focus of this paper.

  11. Differential effect of dark rearing on long-term potentiation induced by layer IV and white matter stimulation in rat visual cortex.

    PubMed

    Salami, M; Fathollahi, Y; Semnanian, S; Atapour, N

    2000-12-01

    In the earlier work, we showed that primed-burst stimulation (PBs) is an effective protocol to induce long-term potentiation (LTP) in layer II/III of adult rat visual cortex in vitro. In the present study, we investigated effects of dark rearing on potentiation of layer II/III responses to stimulation of layer IV or the underlying white matter in the visual cortex in vitro. Long-term potentiation was induced by PBs applied to white matter or layer IV of the cortex in light and dark reared rats. Regardless of the stimulation site, layer II/III field potentials consisted of two components. In general, the latency of responses in dark reared rats was shorter than that in light reared ones. Whereas PBs of layer IV produced LTP of two components in both the groups, that of white matter induced an appreciable potentiation of the second component in both groups and the first component only in dark reared rats. These results indicate that PBs of either white matter or layer IV can gain access to the modifiable synapses that are related to the second component of layer II/III responses in light and dark reared visual cortex, but accessibility of the modifiable synapses that are related to first component depends on the tetanization site. The dark rearing enhances accessibility of the modifiable synapses that are related to the first component following PBs of the white matter. It is suggested that the immaturity of inhibitory circuits and/or better function of excitatory ones in the visual cortex of dark reared rats may contribute to the enhanced accessibility of the first component.

  12. Inhibition of hippocampal long-term potentiation by high-fat diets: is it related to an effect of palmitic acid involving glycogen synthase kinase-3?

    PubMed

    Contreras, Ana; Del Rio, Danila; Martínez, Ana; Gil, Carmen; Morales, Lidia; Ruiz-Gayo, Mariano; Del Olmo, Nuria

    2017-04-12

    High-fat diets (HFD) impair hippocampal-dependent learning and memory and produce important changes in synaptic transmission by enhancing glutamate uptake, decreasing synaptic efficacy, and inhibiting plasticity mechanisms such as N-methyl-D-aspartate-mediated long-term depression (LTD) within the hippocampus. Adolescent animals seem to be particularly susceptible to the detrimental effect of HFD as dietary treatments carried out between weaning and early adulthood are much more efficient in terms of hippocampal damage that those carried out during the adult period. As palmitic acid is the most abundant saturated fatty acid in HFD, its effect on hippocampal function needs to be studied. However, glycogen synthase kinase-3 (GSK-3), a pleiotropic enzyme highly expressed in the central nervous system, modulates both hippocampal long-term potentiation (LTP) and LTD, and has been implicated in neurological disorders including Alzheimer's disease. In this study, we have characterized in mice hippocampus the effect of (i) a 48 h HFD intervention and (ii) in-vitro palmitic acid, as well as the possible involvement of GSK-3 in the above-mentioned plasticity mechanisms. Our results show that both 48 h HFD and palmitic acid inhibit LTP in hippocampal slices, whereas no effect on LTD was observed. Moreover, tideglusib, an ATP-noncompetitive inhibitor of GSK-3, induced hippocampal LTP and partially reversed the impairment of LTP induced by palmitic acid.

  13. The Kinase Function of MSK1 Regulates BDNF Signaling to CREB and Basal Synaptic Transmission, But Is Not Required for Hippocampal Long-Term Potentiation or Spatial Memory

    PubMed Central

    Daumas, Stephanie; Hunter, Christopher J.; Mistry, Rajen B.; Cooper, Daniel D.; Reyskens, Kathleen M.; Flynn, Harry T.

    2017-01-01

    Abstract The later stages of long-term potentiation (LTP) in vitro and spatial memory in vivo are believed to depend upon gene transcription. Accordingly, considerable attempts have been made to identify both the mechanisms by which transcription is regulated and indeed the gene products themselves. Previous studies have shown that deletion of one regulator of transcription, the mitogen- and stress-activated kinase 1 (MSK1), causes an impairment of spatial memory. Given the ability of MSK1 to regulate gene expression via the phosphorylation of cAMP response element binding protein (CREB) at serine 133 (S133), MSK1 is a plausible candidate as a prime regulator of transcription underpinning synaptic plasticity and learning and memory. Indeed, prior work has revealed the necessity for MSK1 in homeostatic and experience-dependent synaptic plasticity. However, using a knock-in kinase-dead mouse mutant of MSK1, the current study demonstrates that, while the kinase function of MSK1 is important in regulating the phosphorylation of CREB at S133 and basal synaptic transmission in hippocampal area CA1, it is not required for metabotropic glutamate receptor-dependent long-term depression (mGluR-LTD), two forms of LTP or several forms of spatial learning in the watermaze. These data indicate that other functions of MSK1, such as a structural role for the whole enzyme, may explain previous observations of a role for MSK1 in learning and memory. PMID:28275711

  14. Long-term potentiation of evoked presynaptic response at CA3-CA1 synapses by transient oxygen-glucose deprivation in rat brain slices.

    PubMed

    Ai, Jinglu; Baker, Andrew

    2006-02-01

    Physiological activity-dependent long-term changes in synaptic transmission, as long-term potentiation (LTP) are thought to be the substrate of learning and memory. However, a form of postsynaptic pathological LTP at the CA3-CA1 synapses has been demonstrated following few minutes of anoxia and aglycemia in vitro. The ischemia LTP shared many molecular mechanisms with the physiological LTP, and was believed to be involved in the delayed neuronal death following ischemia. However, the role of the presynaptic component in this regard is not known. Here we show that a short period of oxygen-glucose deprivation can induce a form of LTP (lasting for hours) of the presynaptic response at the CA3-CA1 synapses. This form of LTP is independent of postsynaptic alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors, but Ca(2+) dependent. This presynaptic LTP may represent a presynaptic hyperexcitability of the afferent fibers following ischemia, and responsible for the excitotoxicity to the CA1 neurons (ischemia-induced increases of glutamate release that kills neurons) and the postsynaptic pathological ischemic LTP.

  15. Long-term operation of biological activated carbon pre-treatment for microfiltration of secondary effluent: Correlation between the organic foulants and fouling potential.

    PubMed

    Pramanik, Biplob Kumar; Roddick, Felicity A; Fan, Linhua

    2016-03-01

    The impact of long-term (>2 years) biological activated carbon (BAC) treatment for mitigating organic fouling in the microfiltration of biologically treated secondary effluent was investigated. Correlation between the organic constituents and hydraulic filtration resistance was investigated to identify the major components responsible for fouling. Over two years operation, the removal efficiency for dissolved organic carbon (DOC) by the BAC treatment was fairly consistent (30 ± 3%), although the reduction in UVA254 gradually decreased from 56 to 34%. BAC treatment effectively decreased the organic foulants in the effluent and so contributed to the mitigation of membrane fouling as shown by reduction in the unified membrane fouling index (UMFI). BAC consistently removed biopolymers whereas the removal of humic substances decreased from 52 to 25% after two years of BAC operation, and thus led to a gradual decrease in UMFI reduction efficiency from 78 to 43%. This was due to gradual reduction in adsorption capacity of the activated carbon as confirmed by analysis of its pore size distribution. Hence humics also played an important role in membrane fouling. However, there was a good correlation between protein and carbohydrate contents with hydraulically reversible and irreversible filtration resistance, compared with UVA254, turbidity and DOC. Although the mitigation of membrane fouling decreased over time, this study demonstrated that the long-term use of BAC pre-treatment of biologically treated secondary effluent prior to microfiltration has potential to reduce the need for frequent chemical cleaning and so increase membrane life span.

  16. Spatial performance in a complex maze is associated with persistent long-term potentiation enhancement in mouse hippocampal slices at early training stages.

    PubMed

    Lange-Asschenfeldt, C; Lohmann, P; Riepe, M W

    2007-06-29

    Long-term potentiation (LTP) and long-term depression (LTD) are principal reflections of synaptic plasticity that have been implicated in learning and memory. We have previously shown that spatial learning in a newly validated complex maze is accompanied by depression of hippocampal CA1 synaptic activity in hippocampal slices of trained mice ("behavioral LTD"). In the present study, we investigated whether behavioral LTD is accompanied by alterations of subsequent LTP induced by high-frequency stimulation (HFS). Moreover, we were interested in the time course of such alterations in relation to training stage. Animals underwent 1, 2, and 8 days of spatial training in the complex maze, respectively. Hippocampal slices were taken 24 h after the last training session. We found a simultaneous decrease of basal synaptic response and increase of HFS induced LTP magnitude compared with slices of untrained animals. Synaptic plasticity was not influenced by repeated running wheel exercise in an additional control group without spatial learning. The mentioned alterations occurred already after day 2 of maze exploration parallel to the most pronounced improvement of behavioral performance but did not change thereafter until day 8 despite further learning progress. They were also found when animals were trained for 2 days and kept at rest for a subsequent 6 days. In conclusion, spatial learning may be reflected by distinct and persistent measurable alterations of synaptic plasticity in hippocampal CA1 neurons at early training stages.

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

    PubMed

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

    2017-02-01

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

  18. Juvenile flatfish in the northern Baltic Sea - long-term decline and potential links to habitat characteristics

    NASA Astrophysics Data System (ADS)

    Jokinen, Henri; Wennhage, Håkan; Ollus, Victoria; Aro, Eero; Norkko, Alf

    2016-01-01

    Flatfish in the northern Baltic Sea are facing multiple environmental pressures due to on-going large-scale ecosystem changes linked to eutrophication and climate change. Shallow juvenile habitats of flatfishes are expected to be especially susceptible to these environmental pressures. Using previously unpublished historical and present-state data on juvenile flatfish in nursery areas along the Finnish coast we demonstrate a drastic (up to 40 ×) decline in 1-Y-O flounder densities since the 1980s and a particularly low current occurrence of both flounders and turbots in several known juvenile habitats. As a consequence of ongoing coastal eutrophication vegetation coverage and filamentous algae have generally increased in shallow areas. We examined the predicted negative effect of vegetation/algae by exploring quantitative relationships between juvenile flatfish (flounder and turbot) occurrence and vegetation/algae among other environmental factors in shallow juvenile habitats. Despite sparse occurrence of juveniles we found a significant negative relationship between flatfish abundance and vegetation cover, implicating eutrophication as a potential major driver affecting the value of juvenile habitat. Shallow littoral habitats play a particularly central role for flatfish due to the spatial concentration of fish in these areas during the critical juvenile stage. Despite their importance, these areas have been relatively poorly studied in the northern Baltic Sea, which makes it difficult to quantify overall changes in environmental conditions and to relate these changes to flatfish recruitment. The low present-state flatfish densities recorded preclude strong inferences of the role of habitat quality to be drawn. Our study does, however, provide a baseline for future assessment. Based on existing evidence, we cannot thus establish any bottlenecks but hypothesize that the current low occurrence of juvenile flatfish, and the population decline of flounder on the

  19. Japan's Long-term Energy Demand and Supply Scenario to 2050 - Estimation for the Potential of Massive CO2 Mitigation

    SciTech Connect

    Komiyama, Ryoichi; Marnay, Chris; Stadler, Michael; Lai, Judy; Borgeson, Sam; Coffey, Brian; Azevedo, Ines Lima

    2009-09-01

    In this analysis, the authors projected Japan's energy demand/supply and energy-related CO{sub 2} emissions to 2050. Their analysis of various scenarios indicated that Japan's CO{sub 2} emissions in 2050 could be potentially reduced by 26-58% from the current level (FY 2005). These results suggest that Japan could set a CO{sub 2} emission reduction target for 2050 at between 30% and 60%. In order to reduce CO{sub 2} emissions by 60% in 2050 from the present level, Japan will have to strongly promote energy conservation at the same pace as an annual rate of 1.9% after the oil crises (to cut primary energy demand per GDP (TPES/GDP) in 2050 by 60% from 2005) and expand the share of non-fossil energy sources in total primary energy supply in 2050 to 50% (to reduce CO{sub 2} emissions per primary energy demand (CO{sub 2}/TPES) in 2050 by 40% from 2005). Concerning power generation mix in 2050, nuclear power will account for 60%, solar and other renewable energy sources for 20%, hydro power for 10% and fossil-fired generation for 10%, indicating substantial shift away from fossil fuel in electric power supply. Among the mitigation measures in the case of reducing CO{sub 2} emissions by 60% in 2050, energy conservation will make the greatest contribution to the emission reduction, being followed by solar power, nuclear power and other renewable energy sources. In order to realize this massive CO{sub 2} abatement, however, Japan will have to overcome technological and economic challenges including the large-scale deployment of nuclear power and renewable technologies.

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

    PubMed

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

    2015-11-01

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

  1. Long-term low-dose α-particle enhanced the potential of malignant transformation in human bronchial epithelial cells through MAPK/Akt pathway

    SciTech Connect

    Liu, Weili; Xiao, Linlin; Dong, Chen; He, Mingyuan; Pan, Yan; Xie, Yuexia; Tu, Wenzhi; Fu, Jiamei; Shao, Chunlin

    2014-05-09

    Highlights: • Multi-exposures of 25 mGy α-ray enhanced cell proliferation, adhesion, and invasion. • MAPK/Akt but not JNK/P66 was positively correlated with cell invasive phenotypes. • LDR of α-irradiation triggers cell malignant transformation through MAPK/Akt. - Abstract: Since the wide usage of ionizing radiation, the cancer risk of low dose radiation (LDR) (<0.1 Gy) has become attractive for a long time. However, most results are derived from epidemiologic studies on atomic-bomb survivors and nuclear accidents surrounding population, and the molecular mechanism of this risk is elusive. To explore the potential of a long-term LDR-induced malignant transformation, human bronchial epithelial cells Beas-2B were fractionally irradiated with 0.025 Gy α-particles for 8 times in total and then further cultured for 1–2 months. It was found that the cell proliferation, the abilities of adhesion and invasion, and the protein expressions of p-ERK, p-Akt, especially p-P38 were not only increased in the multiply-irradiated cells but also in their offspring 1–2 months after the final exposure, indicating high potentiality of cell malignant transformation. On opposite, the expressions of p-JNK and p-P66 were diminished in the subcultures of irradiated cells and thus may play a role of negative regulation in canceration. When the cells were transferred with p38 siRNA, the LDR-induced enhancements of cell adhesion and invasion were significantly reduced. These findings suggest that long-term LDR of α-particles could enhance the potential of malignant transformation incidence in human bronchial epithelial cells through MAPK/Akt pathway.

  2. Meditation and attention: A controlled study on long-term meditators in behavioral performance and event-related potentials of attentional control.

    PubMed

    Jo, Han-Gue; Schmidt, Stefan; Inacker, Elisa; Markowiak, Michael; Hinterberger, Thilo

    2016-01-01

    Meditation practice involves attention regulation, and thus is thought to facilitate attention control mechanisms. Studies on meditation techniques using a behavioral measurement of the Attention Network Test (ANT) have shown enhanced attention control, but neural features remain unknown. In the present study, event-related potentials (ERPs) and behavioral data from twenty long-term meditators were examined, compared to data obtained from twenty matched controls. Results showed that meditators made fewer error responses than controls, especially during the incongruent target condition, suggesting higher accuracy in executive attention control among meditators. The P3 amplitude in the parietal area remained constant in the congruent and incongruent target conditions among meditators, indicating a higher parietal P3 amplitude during the incongruent target condition relative to matched controls. The findings that meditators exhibited fewer error responses on the ANT and a lack of parietal P3 modulation irrespective of reaction time are discussed in the context of attentional resource allocation.

  3. Long-Term Potentiation at CA3–CA1 Hippocampal Synapses with Special Emphasis on Aging, Disease, and Stress

    PubMed Central

    Kumar, Ashok

    2011-01-01

    Synaptic plasticity in the mammalian central nervous system has been the subject of intense investigation for the past four decades. Long-term potentiation (LTP), a major reflection of synaptic plasticity, is an activity-driven long-lasting increase in the efficacy of excitatory synaptic transmission following the delivery of a brief, high-frequency train of electrical stimulation. LTP is regarded as a principal candidate for the cellular mechanisms involved in learning and offers an attractive hypothesis of how memories are constructed. There are a number of exceptional full-length reviews published on LTP; the current review intends to present an overview of the research findings regarding hippocampal LTP with special emphasis on aging, diseases, and psychological insults. PMID:21647396

  4. Neuronal expression of the ubiquitin E3 ligase APC/C-Cdh1 during development is required for long-term potentiation, behavioral flexibility, and extinction.

    PubMed

    Pick, Joseph E; Wang, Li; Mayfield, Joshua E; Klann, Eric

    2013-02-01

    Cdh1 is a regulatory subunit of the Anaphase Promoting Complex/Cyclosome (APC/C), a ubiquitin E3 ligase known to be involved in regulating cell cycle progression. Recent studies have demonstrated a role for Cdh1 in neurons during developmental and adult synaptic plasticity, as well as memory. In order to better characterize the contribution of Cdh1 in synaptic plasticity and memory, we generated conditional knockout mice using a neuron-specific enolase (Nse) promoter where Cdh1 was eliminated in neurons from the onset of differentiation. Although we detected impaired long-term potentiation (LTP) in hippocampal slices from the Nse-Cdh1 knockout (KO) mice, performance on several hippocampus-dependent memory tasks remained intact. However, the Nse-Cdh1 KO mice exhibited impaired behavioral flexibility and extinction of previously consolidated memories. These findings suggest a role for Cdh1 in regulating the updating of consolidated memories.

  5. M2 muscarinic acetylcholine receptors regulate long-term potentiation at hippocampal CA3 pyramidal cell synapses in an input-specific fashion.

    PubMed

    Zheng, Fang; Wess, Jürgen; Alzheimer, Christian

    2012-07-01

    Muscarinic receptors have long been known as crucial players in hippocampus-dependent learning and memory, but our understanding of the cellular underpinnings and the receptor subtypes involved lags well behind. This holds in particular for the hippocampal CA3 region, where the mechanisms of synaptic plasticity depend on the type of afferent input. Williams and Johnston (Williams S, Johnston D. Science 242: 84-87, 1988; Williams S, Johnston D. J Neurophysiol 64: 1089-1097, 1990) demonstrated muscarinic depression of mossy fiber (MF) long-term potentiation (LTP) through a presynaptic site of action and Maeda et al. (Maeda T, Kaneko S, Satoh M. Brain Res 619: 324-330, 1993) proposed a bidirectional modulation of MF LTP by muscarinic receptor subtypes. Since then, this issue, as well as muscarinic regulation of plasticity at associational/commissural (A/C) fiber-CA3 synapses has remained largely neglected, not least because of the lack of highly selective ligands for the different muscarinic receptor subtypes. In the present study, we performed field potential and whole cell recordings from the hippocampal CA3 region of M(2) receptor knockout mice to determine the role of M(2) receptors in short-term and long-term plasticity at A/C and MF inputs to CA3 pyramidal cells. At the A/C synapse, M(2) receptors promoted short-term facilitation and LTP. Unexpectedly, M(2) receptors mediated the opposite effect on LTP at the MF synapse, which was significantly reduced, most likely involving a depressant effect of M(2) receptors on adenylyl cyclase activity in MF terminals. Our data demonstrate that cholinergic projections recruit M(2) receptors to redistribute the gain of LTP in CA3 pyramidal cells in an input-specific manner.

  6. Disruption of hippocampal synaptic transmission and long-term potentiation by psychoactive synthetic cannabinoid 'Spice' compounds: comparison with Δ(9) -tetrahydrocannabinol.

    PubMed

    Hoffman, Alexander F; Lycas, Matthew D; Kaczmarzyk, Jakub R; Spivak, Charles E; Baumann, Michael H; Lupica, Carl R

    2017-03-01

    There has been a marked increase in the availability of synthetic drugs designed to mimic the effects of marijuana. These cannabimimetic drugs, sold illicitly as 'Spice' and related products, are associated with serious medical complications in some users. In vitro studies suggest that synthetic cannabinoids in these preparations are potent agonists at central cannabinoid CB1 receptors (CB1Rs), but few investigations have delineated their cellular effects, particularly in comparison with the psychoactive component of marijuana, Δ(9) -tetrahydrocannabinol (Δ(9) -THC). We compared the ability of three widely abused synthetic cannabinoids and Δ(9) -THC to alter glutamate release and long-term potentiation in the mouse hippocampus. JWH-018 was the most potent inhibitor of hippocampal synaptic transmission (EC50 ~15 nM), whereas its fluoropentyl derivative, AM2201, inhibited synaptic transmission with slightly lower potency (EC50 ~60 nM). The newer synthetic cannabinoid, XLR-11, displayed much lower potency (EC50 ~900 nM) that was similar to Δ(9) -THC (EC50 ~700 nM). The effects of all compounds occurred via activation of CB1Rs, as demonstrated by reversal with the selective antagonist/inverse agonist AM251 or the neutral CB1R antagonist PIMSR1. Moreover, AM2201 was without effect in the hippocampus of transgenic mice lacking the CB1R. Hippocampal slices exposed to either synthetic cannabinoids or Δ(9) -THC exhibited significantly impaired long-term potentiation (LTP). We find that, compared with Δ(9) -THC, the first-generation cannabinoids found in Spice preparations display higher potency, whereas a recent synthetic cannabinoid is roughly equipotent with Δ(9) -THC. The disruption of synaptic function by these synthetic cannabinoids is likely to lead to profound impairments in cognitive and behavioral function.

  7. Induction of rhodanese, a detoxification enzyme, in livers from mice after long-term irradiation with low-dose-rate gamma-rays.

    PubMed

    Nakajima, Tetsuo; Taki, Keiko; Wang, Bing; Ono, Tetsuya; Matsumoto, Tsuneya; Oghiso, Yoichi; Tanaka, Kimio; Ichinohe, Kazuaki; Nakamura, Shingo; Tanaka, Satoshi; Nenoi, Mitsuru

    2008-11-01

    The health effects of low-dose radiation exposure are of public concern. Although molecular events in the cellular response to high-dose-rate radiation exposure have been fully investigated, effects of long-term exposure to extremely low-dose-rate radiation remain unclear. Protein expression was analyzed by two-dimensional electrophoresis in livers from mice irradiated for 485 days (22 hr/day) at low-dose-rates of 0.032 microGy/min, 0.65 microGy/min and 13 microGy/min (total doses of 21 mGy, 420 mGy and 8000 mGy, respectively). One of the proteins that showed marked changes in expression was identified as rhodanese (thiosulfate sulfurtransferase). Rhodanese expression was increased after irradiation at 0.65 microGy/min and 13 microGy/min, while its expression was not changed at 0.032 microGy/min. Rhodanese is a detoxification enzyme, probably related to the regulation of antioxidative function. However, antioxidative proteins, such as superoxide dismutase (SOD)1 (also known as Cu,Zn-SOD) and SOD2 (also known as Mn-SOD), which can be induced by high-dose-rate radiation, were not induced at any low-dose-rates tested. These findings indicate that rhodanese is a novel protein induced by low-dose-rate radiation, and further analysis could provide insight into the effects of extremely low-dose-rate radiation exposure.

  8. Observed and Potential Responses of Upland Tundra Ecosystems to a Changing Climate: Results from the Arctic Long-Term Ecological Research Project, North Slope, Alaska, USA

    NASA Astrophysics Data System (ADS)

    Bowden, W. B.

    2014-12-01

    The Arctic is one of the most rapidly changing biomes on earth. Research at the Toolik Field Station by the Arctic Long-Term Ecological Research project provides a perspective on changes that are impacting the upland tussock tundra region of the North Slope of Alaska, a region that is typical of ~15% of the arctic region. The arctic is responding to a combination of long-term, gradual changes (presses) and short-term, event-driven changes (pulses). The most important press, of course, is the persistent rise in average annual air temperature observed in most places (though not at Toolik). Associated with this increase in SAT is a well-documented increase in shallow permafrost temperature (which is observed around Toolik). Our long-term research shows that this trend will favor taller and more productive shrub and grass vegetation. Higher SAT translates to earlier spring breakup and later onset of winter. This change in seasonality is affecting interactions between shrub leaf-out, insect emergence, and bird nesting. Persistent and more frequent droughts are having important impacts on the ability of Arctic grayling - the top consumer is most upland tundra streams - to survive and has the potential to block their ability to migrate to essential overwintering lakes. The interaction between temperature (which is changing) and light (which is not) creates a "seasonal asynchrony" that may be increasing the loading of nutrients - notably nitrate - to upland tundra streams late in the season, with impacts that we do not fully understand yet. The upland tundra environment is also responding to an increasing frequency of pulses, most notably wildfires and the development of thermo-erosional failures (TEFs). Wildfires transfer large quantities of carbon and nitrogen directly to the atmosphere. TEFs may deliver large quantities of sediment and nutrients to streams and lakes. Currently these pulse disturbances seem to be having only limited, local impacts. However, as shallow

  9. Effects of Joint Attention on Long-Term Memory in 9-Month-Old Infants: An Event-Related Potentials Study

    ERIC Educational Resources Information Center

    Kopp, Franziska; Lindenberger, Ulman

    2011-01-01

    Joint attention develops during the first year of life but little is known about its effects on long-term memory. We investigated whether joint attention modulates long-term memory in 9-month-old infants. Infants were familiarized with visually presented objects in either of two conditions that differed in the degree of joint attention (high…

  10. Intraoperative Motor-Evoked Potential Disappearance versus Amplitude-Decrement Alarm Criteria During Cervical Spinal Surgery: A Long-Term Prognosis

    PubMed Central

    Kim, Dong-Gun; Choi, Young-Doo; Jin, Seung-Hyun; Kim, Chi Heon; Lee, Kwang-Woo; Park, Kyung Seok

    2017-01-01

    Background and Purpose We studied the clinical significance of amplitude-reduction and disappearance alarm criteria for transcranial electric muscle motor-evoked potentials (MEPs) during cervical spinal surgery according to different lesion locations [intramedullary (IM) vs. nonintramedullary (NIM)] by evaluating the long-term postoperative motor status. Methods In total, 723 patients were retrospectively dichotomized into the IM and NIM groups. Each limb was analyzed respectively. One hundred and sixteen limbs from 30 patients with IM tumors and 2,761 limbs from 693 patients without IM tumors were enrolled. Postoperative motor deficits were assessed up to 6 months after surgery. Results At the end of surgery, 61 limbs (2.2%) in the NIM group and 14 limbs (12.1%) in the IM group showed MEP amplitudes that had decreased to below 50% of baseline, with 13 of the NIM limbs (21.3%) and 2 of the IM limbs (14.3%) showing MEP disappearance. Thirteen NIM limbs (0.5%) and 5 IM limbs (4.3%) showed postoperative motor deficits. The criterion for disappearance showed a lower sensitivity for the immediate motor deficit than did the criterion for amplitude decrement in both the IM and NIM groups. However, the disappearance criterion showed the same sensitivity as the 70%-decrement criterion in IM (100%) and NIM (83%) surgeries for the motor deficit at 6 months after surgery. Moreover, it has the highest specificity for the motor deficits among diverse alarm criteria, from 24 hours to 6 months after surgery, in both the IM and NIM groups. Conclusions The MEP disappearance alarm criterion had a high specificity in predicting the long-term prognosis after cervical spinal surgery. However, because it can have a low sensitivity in predicting an immediate postoperative deficit, combining different MEP alarm criteria according to the aim of specific instances of cervical spinal surgery is likely to be useful in practical intraoperative monitoring. PMID:27730765

  11. Evaluation of a deposit in the vicinity of the PBU L-106 Site, North Slope, Alaska, for a potential long-term test of gas production from hydrates

    SciTech Connect

    Moridis, G.J.; Reagan, M.T.; Boyle, K.L.; Zhang, K.

    2010-05-01

    As part of the effort to investigate the technical feasibility of gas production from hydrate deposits, a long-term field test (lasting 18-24 months) is under consideration in a project led by the U.S. Department of Energy. We evaluate a candidate deposit involving the C-Unit in the vicinity of the PBU-L106 site in North Slope, Alaska. This deposit is stratigraphically bounded by impermeable shale top and bottom boundaries (Class 3), and is characterized by high intrinsic permeabilities, high porosity, high hydrate saturation, and a hydrostatic pressure distribution. The C-unit deposit is composed of two hydrate-bearing strata separated by a 30-ft-thick shale interlayer, and its temperatrure across its boundaries ranges between 5 and 6.5 C. We investigate by means of numerical simulation involving very fine grids the production potential of these two deposits using both vertical and horizontal wells. We also explore the sensitivity of production to key parameters such as the hydrate saturation, the formation permeability, and the permeability of the bounding shale layers. Finally, we compare the production performance of the C-Unit at the PBU-L106 site to that of the D-Unit accumulation at the Mount Elbert site, a thinner, single-layer Class 3 deposit on the North Slope of Alaska that is shallower, less-pressurized and colder (2.3-2.6 C). The results indicate that production from horizontal wells may be orders of magnitude larger than that from vertical ones. Additionally, production increases with the formation permeability, and with a decreasing permeability of the boundaries. The effect of the hydrate saturation on production is complex and depends on the time frame of production. Because of higher production, the PBU-L106 deposit appears to have an advantage as a candidate for the long-term test.

  12. Potential Role for Mycobacterium tuberculosis Specific IL-2 and IFN-γ Responses in Discriminating between Latent Infection and Active Disease after Long-Term Stimulation

    PubMed Central

    Sun, Qin; Wei, Wei; Sha, Wei

    2016-01-01

    Interferon gamma release assays (IGRAs) could accurately diagnose Mycobacterium tuberculosis (M.tuberculosis) infection. However, these assays do not discriminate between latent tuberculosis infection (LTBI) and active tuberculosis disease (ATB). Here, a total of 177 subjects, including 65 patients with ATB, 43 subjects with LTBI, and 69 TB-uninfected controls (CON group) were enrolled. The concentration of IFN-γ, IP-10, and IL-2 was determined in peripheral blood mononuclear cells (PBMCs) after short-term (24h) or long-term (72h) stimulation with TB antigens including ESAT-6/CFP-10 (EC) and purified protein derivative (PPD).EC-stimulated IL-2 and gamma interferon-inducible protein 10 (IP-10) release (24h and 72h) showed a good diagnostic performance in distinguishing between TB-infected and TB-uninfected individuals, but failed to discriminate between ATB and LTBI. After 72h of incubation, the release of IL-2 was higher in LTBI patients after stimulation with EC and PPD. The PPD-stimulated IL-2/IFN-γ ratio after 72h incubation had the diagnostic potential to discriminate between ATB and LTBI, with a sensitivity of 90.8% and a specificity of 97.7%. In addition, these new biomarkers, combined with T-SPOT test in a two-step strategy, were validated with high levels of accuracy in a prospective clinical-based cohort. Collectively, the PPD-stimulated IL-2/IFN-γ ratio after long-term incubation may be an alternative diagnostic biomarker in distinguishing between active TB patients and subjects with latent infection. PMID:28033330

  13. Subchronic MK-801 treatment and post-weaning social isolation in rats: differential effects on locomotor activity and hippocampal long-term potentiation.

    PubMed

    Ashby, Donovan M; Habib, Diala; Dringenberg, Hans C; Reynolds, James N; Beninger, Richard J

    2010-09-01

    Subchronic NMDA receptor antagonist treatment and post-weaning social isolation are two animal models of schizophrenia symptoms. However, behavioral and physiological changes following a combination of these two procedures have not been investigated. Thus, we examined effects of a novel, "double hit" model combining these two treatments, comparing them to standard models involving only NMDA antagonist treatment or social isolation. Male, Sprague-Dawley rats were either group-housed or maintained in social isolation (starting at postnatal day [PD] 21 and continuing throughout the study). Each housing condition was further subdivided into two groups, receiving either subchronic treatment with either saline or MK-801 (0.5mg/kg, i.p., 2xday for seven days starting at PD 56). Post-weaning social isolation increased locomotor activity (assessed at PD 70) in response to a novel environment and an acute amphetamine injection, while subchronic MK-801 increased only amphetamine induced locomotor activity. Subsequent electrophysiological experiments (under urethane anesthesia) assessing changes in plasticity of hippocampal synapses showed that subchronic MK-801 treatment resulted in an increase in long-term potentiation in area CA1 in response to high frequency stimulation of the contralateral CA3 area, while housing condition had no effect. No other changes in hippocampal electrophysiology (input-output curves, paired-pulse facilitation) were observed. These data are the first to demonstrate an enhancement in hippocampal long-term plasticity in vivo following subchronic MK-801 administration, an effect that may be related to the well-characterized changes in glutamatergic and GABAergic systems seen after subchronic NMDA receptor blockade. That lack of additive or synergistic effects in the "double hit model" suggests that combining isolation and subchronic MK-801 treatment does not necessarily produce greater behavioral or physiological dysfunction than that seen with either

  14. Rescue of Cyclic AMP Mediated Long Term Potentiation Impairment in the Hippocampus of Mecp2 Knockout (Mecp2(-/y) ) Mice by Rolipram.

    PubMed

    Balakrishnan, Saju; Niebert, Marcus; Richter, Diethelm W

    2016-01-01

    Rett syndrome (RTT) patients experience learning difficulties and memory loss. Analogous deficits of hippocampal plasticity are reported in mouse models of RTT. To elucidate the underlying pathophysiology, we studied long term potentiation (LTP) at the CA3 to CA1 synapses in the hippocampus in acute brain slices from WT and Mecp2(-/y) mice, by either activating cAMP dependent pathway or using high frequency stimulation, by means of patch clamp. We have observed that, the NMDA channel current characteristics remain unchanged in the Mecp2(-/y) mice. The adenylyl cyclase (AC) agonist forskolin evoked a long lasting potentiation of evoked EPSCs in WT CA1 neurons, but only minimally enhanced the EPSCs in the Mecp2(-/y) mice. This weaker potentiation in Mecp2 (-/) (y) mice was ameliorated by application of phosphodiesterase 4 inhibitor rolipram. The hyperpolarization activated cyclic nucleotide gated channel current (I h) was potentiated to similar extent by forskolin in both phenotypes. Multiple tetanus induced cAMP-dependent plasticity was also impaired in the Mecp2 (-/) (y) mice, and was also partially rescued by rolipram. Western blot analysis of CA region of Mecp2 (-/) (y) mice hippocampus revealed more than twofold up-regulation of protein kinase A (PKA) regulatory subunits, while the expression of the catalytic subunit remained unchanged. We hypothesize that the overexpressed PKA regulatory subunits buffer cAMP and restrict the PKA mediated phosphorylation of target proteins necessary for LTP. Blocking the degradation of cAMP, thereby saturating the regulatory subunits alleviated this defect.

  15. Nitrogen transformations in a Vertisol under long-term tillage and no tillage management in dryland agricultual systems: key genes and potential rates

    NASA Astrophysics Data System (ADS)

    Melero, Sebastiana; Perez de Mora, Alfredo; Murillo, J. Manuel; Buegger, Franz; Kleinedam, Kristina; Kublik, Susanne; Vanderlinden, Karl; Moreno, Felix; Schloter, Michael

    2010-05-01

    The impact of tillage practices on microbial N transformations in semiarid regions is poorly understood and data from long-term field experiments are scarce. In this study, we evaluated the effects of traditional tillage (TT) vs no-tillage (NT) on key processes of the N cycle such as nitrification and denitrification in a long-term field experiment under a rainfed crop rotation system (cereal-sunflower-legumes) on a vertisol (SW Spain). Besides general soil chemical and biological parameters, we quantified the size of the ammonia oxidizing and denitrifying bacterial populations via real-time PCR (amoA, nirS and nosZ genes), and measured potential nitrification and denitrification rates. Soil was sampled at two depths (0-30, till layer; and 30-50 cm), once during the growing period of the crop (wheat) and another time after harvesting. Conservation tillage slightly increased total organic carbon and microbial biomass C content, whereas no effect on nutrient availability (C and N) was observed, likely due to the fertilization regime and the textural characteristics of the soil type (Vertisol). Gene abundance and potential rates were influenced by the interaction between tillage treatment and sampling period, mainly at 0-30 cm depth. In general, ammonia oxidizers and potential nitrification were enhanced under TT, particularly after harvesting. By contrast, higher abundance of denitrifiers, as reflected by both nirS and nosZ gene copy numbers and larger potential denitrification rates were found under NT during the growing period, but not after harvesting. Results also showed that the N2O/N2 ratio was constant throughout the experiment and thus was affected more significantly by environmental parameters such as the availability carbon than by changes in denitrifier abundance. Our results stress the importance of quantifying microbial populations to address the impact of agricultural practices on N transformations in soil. Furthermore, results suggest that the spatial

  16. Review article: the long-term management of ulcerative colitis.

    PubMed

    Hanauer, S B

    2004-10-01

    After the induction of remission, the second priority of therapy for ulcerative colitis is sustained clinical remission, defined as the absence of inflammatory symptoms (diarrhoea, bleeding, rectal urgency) and the maintenance of an intact mucosa, with the absence of ulcers, friability or significant granularity at endoscopy. The 'optimal' maintenance strategy will depend on the therapy needed to induce remission. Thus, the transition from induction to maintenance therapy will be determined by the intensity of acute therapy necessary to induce remission and the duration of therapy required to complete the resolution of clinical symptoms. There are few controlled clinical trials pertaining to maintenance after each induction regimen. However, experience dictates that aminosalicylates are efficacious after aminosalicylate-induced remissions, that steroids should be tapered according to the time required to induce remission, that patients requiring ciclosporin will benefit from the addition of long-term immunomodulation with azathioprine or mercaptopurine, and that many patients with distal colitis who require topical mesalazine (mesalamine) will continue to need topical therapy to maintain remission, albeit at reduced frequency. The expectations for maintenance therapy require patient adherence to the prescribed treatment regimen. Patients require education with regard to the long-term goals of maintenance therapy (e.g. prevention of relapse, reduction of long-term complications of disease activity or risks of acute therapy with steroids), and should be warned against the use of nonsteroidal anti-inflammatory drugs and cautioned about the cessation of smoking, when applicable, due to potential risks of relapse or chronic activity.

  17. The protective effect of Borago Officinalis extract on amyloid β (25-35)-induced long term potentiation disruption in the dentate gyrus of male rats.

    PubMed

    Zargooshnia, Somayeh; Shahidi, Siamak; Ghahremanitamadon, Fatemeh; Nikkhah, Ali; Mehdizadeh, Mehdi; Soleimani Asl, Sara

    2015-02-01

    Alzheimer's disease (AD) begins with impairment in synaptic functions before developing into later neurodegeneration and neural loss. In the present study we have examined the protective effects of Borago Officinalis (borage) extract on amyloid β (Aβ)--Induced long term potentiation (LTP) disruption in hippocampal dentate gyrus (DG). Wistar male rats received intrahippocampal (IHP) injection of the Aβ (25-35) and borage extract throughout gestation (100 mg/kg). LTP in perforant path- DG synapses was assessed using electrophysiology method and field excitatory post- synaptic potential (fEPSP) slope and population spike (PS) amplitude were measured by 400 Hz tetanization. Finally, the total thiol content of hippocampus was measured using colorimetric reaction based on the Ellman's method. The results showed that Aβ (25-35) significantly decreased fEPSP slope and SP amplitude comparing with the control and sham group, whereas borage extract administration increased these parameters compared to the Aβ group. Aβ induced a remarkable decrease in total thiol content of hippocampus and borage prevented the decrease of the hippocampal total sulfhydryl (SH) groups. This data suggest that Aβ (25-35) can effectively inhibit LTP in the granular cells of the DG in hippocampus, and borage supplementation reverse the synaptic plasticity in DG following Aβ treatment and that borage consumption may lead to an improvement of AD-induced cognitive dysfunction.

  18. Modulation of DL-. alpha. -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/quisqualate receptors by phospholipase A sub 2 : A necessary step in long-term potentiation

    SciTech Connect

    Massicotte, G.; Baudry, M. ); Vanderklish, P.; Lynch, G. )

    1991-03-01

    The effects of kainate (KA)-induced epileptic seizures on the binding properites of hippocampal glutamate receptors, on the modulation of DL-{alpha}-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/quisqualate receptor by phospholipase A{sub 2} (PLA{sub 2}), and on the formation of long-term potentiation (LTP) were studied in hippocampal membranes and hippocampal slices. Systemic administration of KA produced specific changes in the binding properties of the AMPA/quisqualate receptors and its regulation. Whereas the binding of various ligands to the N-methyl-D-aspartate receptors was not modified by KA treatment, there was a singificant decrease in the maximal number of binding sites for ({sup 3}H)AMPA. The loss of LTP was not due to changes in postsynaptic responses elicited by the bursts that trigger the potentiation effect, thus suggesting that KA treatment disrupts processes that follow N-methyl-D-aspartate receptor activation. Systemic administration of KA was associated with calpain activation as the amount of spectrin breakdown products was increased severalfold in hippocampus but not in cerebellum. Pretreatment of telencephalic membranes with calpain greatly reduced the PLA{sub 2}-induced increase in ({sup 3}H)AMPA binding. The results provide evidence in favor of an essential role of PLA{sub 2} in the development of LTP and suggest that the order of activation of different calcium-dependent processes is critical for producing the final changes underlying LTP.

  19. Long-Term Potentiation at the Mossy Fiber-Granule Cell Relay Invokes Postsynaptic Second-Messenger Regulation of Kv4 Channels.

    PubMed

    Rizwan, Arsalan P; Zhan, Xiaoqin; Zamponi, Gerald W; Turner, Ray W

    2016-11-02

    Mossy fiber afferents to cerebellar granule cells form the primary synaptic relay into cerebellum, providing an ideal site to process signal inputs differentially. Mossy fiber input is known to exhibit a long-term potentiation (LTP) of synaptic efficacy through a combination of presynaptic and postsynaptic mechanisms. However, the specific postsynaptic mechanisms contributing to LTP of mossy fiber input is unknown. The current study tested the hypothesis that LTP induces a change in intrinsic membrane excitability of rat cerebellar granule cells through modification of Kv4 A-type potassium channels. We found that theta-burst stimulation of mossy fiber input in lobule 9 granule cells lowered the current threshold to spike and increases the gain of spike firing by 2- to 3-fold. The change in postsynaptic excitability was traced to hyperpolarizing shifts in both the half-inactivation and half-activation potentials of Kv4 that occurred upon coactivating NMDAR and group I metabotropic glutamatergic receptors. The effects of theta-burst stimulation on Kv4 channel control of the gain of spike firing depended on a signaling cascade leading to extracellular signal-related kinase activation. Under physiological conditions, LTP of synaptically evoked spike output was expressed preferentially for short bursts characteristic of sensory input, helping to shape signal processing at the mossy fiber-granule cell relay.

  20. Short and long term bystander effect induction by fathead minnows (Pimephales promelas, Rafinesque, 1820) injected with environmentally relevant whole body doses of 226Ra.

    PubMed

    Smith, Richard W; Seymour, Colin B; Mothersill, Carmel E

    2013-12-01

    Bystander effect induction by fathead minnows injected with environmentally relevant doses of (226)Ra was investigated. Twenty four h and 6 months after injection with a single dose of 21, 210 or 2100 μBq, fin tissue samples emitted a pro-apoptotic signal, which reduced the clonogenic survival of an apoptosis sensitive reporter cell line. Twenty four h and 10 weeks after injection explants from non-injected bystander fish, swum with the injected fish, also emitted a pro-apoptotic signal. However 6 months after injection the bystander fish to 21 and 210 μBq injected fish emitted an anti-apoptotic signal. This demonstrates that extremely low dose irradiation can have effects outside of the irradiated fish. This has implications for population and ecosystem responses to contamination.

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

    PubMed

    Fernández-Ruiz, Antonio; Makarov, Valeri A; Herreras, Oscar

    2012-01-01

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

  2. Critical involvement of postsynaptic protein kinase activation in long-term potentiation at hippocampal mossy fiber synapses on CA3 interneurons.

    PubMed

    Galván, Emilio J; Cosgrove, Kathleen E; Mauna, Jocelyn C; Card, J Patrick; Thiels, Edda; Meriney, Stephen D; Barrionuevo, Germán

    2010-02-24

    Hippocampal mossy fiber (MF) synapses on area CA3 lacunosum-moleculare (L-M) interneurons are capable of undergoing a Hebbian form of NMDA receptor (NMDAR)-independent long-term potentiation (LTP) induced by the same type of high-frequency stimulation (HFS) that induces LTP at MF synapses on pyramidal cells. LTP of MF input to L-M interneurons occurs only at synapses containing mostly calcium-impermeable (CI)-AMPA receptors (AMPARs). Here, we demonstrate that HFS-induced LTP at these MF-interneuron synapses requires postsynaptic activation of protein kinase A (PKA) and protein kinase C (PKC). Brief extracellular stimulation of PKA with forskolin (FSK) alone or in combination with 1-Methyl-3-isobutylxanthine (IBMX) induced a long-lasting synaptic enhancement at MF synapses predominantly containing CI-AMPARs. However, the FSK/IBMX-induced potentiation in cells loaded with the specific PKA inhibitor peptide PKI(6-22) failed to be maintained. Consistent with these data, delivery of HFS to MFs synapsing onto L-M interneurons loaded with PKI(6-22) induced posttetanic potentiation (PTP) but not LTP. Hippocampal sections stained for the catalytic subunit of PKA revealed abundant immunoreactivity in interneurons located in strata radiatum and L-M of area CA3. We also found that extracellular activation of PKC with phorbol 12,13-diacetate induced a pharmacological potentiation of the isolated CI-AMPAR component of the MF EPSP. However, HFS delivered to MF synapses on cells loaded with the PKC inhibitor chelerythrine exhibited PTP followed by a significant depression. Together, our data indicate that MF LTP in L-M interneurons at synapses containing primarily CI-AMPARs requires some of the same signaling cascades as does LTP of glutamatergic input to CA3 or CA1 pyramidal cells.

  3. Effects of neonatal exposure to the flame retardant tetrabromobisphenol-A, aluminum diethylphosphinate or zinc stannate on long-term potentiation and synaptic protein levels in mice.

    PubMed

    Hendriks, Hester S; Koolen, Lucas A E; Dingemans, Milou M L; Viberg, Henrik; Lee, Iwa; Leonards, Pim E G; Ramakers, Geert M J; Westerink, Remco H S

    2015-12-01

    Brominated flame retardants such as tetrabromobisphenol-A (TBBPA) may exert (developmental) neurotoxic effects. However, data on (neuro)toxicity of halogen-free flame retardants (HFFRs) are scarce. Recent in vitro studies indicated a high neurotoxic potential for some HFFRs, e.g., zinc stannate (ZS), whereas the neurotoxic potential of other HFFRs, such as aluminum diethylphosphinate (Alpi), appears low. However, the in vivo (neuro)toxicity of these compounds is largely unknown. We therefore investigated effects of neonatal exposure to TBBPA, Alpi or ZS on synaptic plasticity in mouse hippocampus. Male C57bl/6 mice received a single oral dose of 211 µmol/kg bw TBBPA, Alpi or ZS on postnatal day (PND) 10. On PND 17-19, effects on hippocampal synaptic plasticity were investigated using ex vivo extracellular field recordings. Additionally, we measured levels of postsynaptic proteins involved in long-term potentiation (LTP) as well as flame retardant concentrations in brain, muscle and liver tissues. All three flame retardants induced minor, but insignificant, effects on LTP. Additionally, TBBPA induced a minor decrease in post-tetanic potentiation. Despite these minor effects, expression of selected synaptic proteins involved in LTP was not affected. The flame retardants could not be measured in significant amounts in the brains, suggesting low bioavailability and/or rapid elimination/metabolism. We therefore conclude that a single neonatal exposure on PND 10 to TBBPA, Alpi or ZS does affect neurodevelopment and synaptic plasticity only to a small extent in mice. Additional data, in particular on persistence, bioaccumulation and (in vivo) toxicity, following prolonged (developmental) exposure are required for further (human) risk assessment.

  4. N-Terminal pyroglutamate formation of Aβ38 and Aβ40 enforces oligomer formation and potency to disrupt hippocampal long-term potentiation.

    PubMed

    Schlenzig, Dagmar; Rönicke, Raik; Cynis, Holger; Ludwig, Hans-Henning; Scheel, Eike; Reymann, Klaus; Saido, Takaomi; Hause, Gerd; Schilling, Stephan; Demuth, Hans-Ulrich

    2012-06-01

    Pyroglutamate (pGlu)-modified amyloid peptides have been identified in sporadic and familial forms of Alzheimer's disease (AD) and the inherited disorders familial British and Danish Dementia (FBD and FDD). In this study, we characterized the aggregation of amyloid-β protein Aβ37, Aβ38, Aβ40, Aβ42 and ADan species in vitro, which were modified by N-terminal pGlu (pGlu-Aβ3-x, pGlu-ADan) or possess the intact N-terminus (Aβ1-x, ADan). The pGlu-modification confers rapid formation of oligomers and short fibrillar aggregates. In accordance with these observations, the pGlu-modified Aβ38, Αβ40 and Αβ42 species inhibit hippocampal long term potentiation of synaptic response, but pGlu-Aβ3-42 showing the highest effect. Among the unmodified Aβ peptides, only Aβ1-42 exhibites such propensity, which was similar to pGlu-Aβ3-38 and pGlu-Aβ3-40. Likewise, the amyloidogenic peptide pGlu-ADan impaired synaptic potentiation more pronounced than N-terminal unmodified ADan. The results were validated using conditioned media from cultivated HEK293 cells, which express APP variants favoring the formation of Aβ1-x, Aβ3-x or N-truncated pGlu-Aβ3-x species. Hence, we show that the ability of different amyloid peptides to impair synaptic function apparently correlates to their potential to form oligomers as a common mechanism. The pGlu-modification is apparently mediating a higher surface hydrophobicity, as shown by 1-anilinonaphtalene-8-sulfonate fluorescence, which enforces potential to interfere with neuronal physiology.

  5. Rescue of Cyclic AMP Mediated Long Term Potentiation Impairment in the Hippocampus of Mecp2 Knockout (Mecp2-/y) Mice by Rolipram

    PubMed Central

    Balakrishnan, Saju; Niebert, Marcus; Richter, Diethelm W.

    2016-01-01

    Rett syndrome (RTT) patients experience learning difficulties and memory loss. Analogous deficits of hippocampal plasticity are reported in mouse models of RTT. To elucidate the underlying pathophysiology, we studied long term potentiation (LTP) at the CA3 to CA1 synapses in the hippocampus in acute brain slices from WT and Mecp2-/y mice, by either activating cAMP dependent pathway or using high frequency stimulation, by means of patch clamp. We have observed that, the NMDA channel current characteristics remain unchanged in the Mecp2-/y mice. The adenylyl cyclase (AC) agonist forskolin evoked a long lasting potentiation of evoked EPSCs in WT CA1 neurons, but only minimally enhanced the EPSCs in the Mecp2-/y mice. This weaker potentiation in Mecp2-/y mice was ameliorated by application of phosphodiesterase 4 inhibitor rolipram. The hyperpolarization activated cyclic nucleotide gated channel current (Ih) was potentiated to similar extent by forskolin in both phenotypes. Multiple tetanus induced cAMP-dependent plasticity was also impaired in the Mecp2-/y mice, and was also partially rescued by rolipram. Western blot analysis of CA region of Mecp2-/y mice hippocampus revealed more than twofold up-regulation of protein kinase A (PKA) regulatory subunits, while the expression of the catalytic subunit remained unchanged. We hypothesize that the overexpressed PKA regulatory subunits buffer cAMP and restrict the PKA mediated phosphorylation of target proteins necessary for LTP. Blocking the degradation of cAMP, thereby saturating the regulatory subunits alleviated this defect. PMID:26869885

  6. Dose-dependent effect of donepezil administration on long-term enhancement of visually evoked potentials and cholinergic receptor overexpression in rat visual cortex.

    PubMed

    Chamoun, Mira; Groleau, Marianne; Bhat, Menakshi; Vaucher, Elvire

    2016-09-01

    Stimulation of the cholinergic system tightly coupled with periods of visual stimulation boosts the processing of specific visual stimuli via muscarinic and nicotinic receptors in terms of intensity, priority and long-term effect. However, it is not known whether more diffuse pharmacological stimulation with donepezil, a cholinesterase inhibitor, is an efficient tool for enhancing visual processing and perception. The goal of the present study was to potentiate cholinergic transmission with donepezil treatment (0.5 and 1mg/kg) during a 2-week visual training to examine the effect on visually evoked potentials and to profile the expression of cholinergic receptor subtypes. The visual training was performed daily, 10min a day, for 2weeks. One week after the last training session, visual evoked potentials were recorded, or the mRNA expression level of muscarinic (M1-5) and nicotinic (α/β) receptors subunits was determined by quantitative RT-PCR. The visual stimulation coupled with any of the two doses of donepezil produced significant amplitude enhancement of cortical evoked potentials compared to pre-training values. The enhancement induced by the 1mg/kg dose of donepezil was spread to neighboring spatial frequencies, suggesting a better sensitivity near the visual detection threshold. The M3, M4, M5 and α7 receptors mRNA were upregulated in the visual cortex for the higher dose of donepezil but not the lower one, and the receptors expression was stable in the somatosensory (non-visual control) cortex. Therefore, higher levels of acetylcholine within the cortex sustain the increased intensity of the cortical response and trigger the upregulation of cholinergic receptors.

  7. Modulation of Long-Term Potentiation of Cortico-Amygdala Synaptic Responses and Auditory Fear Memory by Dietary Polyunsaturated Fatty Acid

    PubMed Central

    Yamada, Daisuke; Wada, Keiji; Sekiguchi, Masayuki

    2016-01-01

    Converging evidence suggests that an imbalance of ω3 to ω6 polyunsaturated fatty acid (PUFA) in the brain is involved in mental illnesses such as anxiety disorders. However, the underlying mechanism is unknown. We previously reported that the dietary ratio of ω3 to ω6 PUFA alters this ratio in the brain, and influences contextual fear memory. In addition to behavioral change, enhancement of cannabinoid CB1 receptor-mediated short-term synaptic plasticity and facilitation of the agonist sensitivity of CB1 receptors have been observed in excitatory synaptic responses in the basolateral nucleus of the amygdala (BLA). However, it is not known whether long-term synaptic plasticity in the amygdala is influenced by the dietary ratio of ω3 to ω6 PUFA. In the present study, we examined long-term potentiation (LTP) of optogenetically-evoked excitatory synaptic responses in synapses between the terminal of the projection from the auditory cortex (ACx) and the pyramidal cells in the lateral nucleus of the amygdala. We found that LTP in this pathway was attenuated in mice fed with a high ω3 to ω6 PUFA ratio diet (0.97), compared with mice fed with a low ω3 to ω6 PUFA ratio diet (0.14). Furthermore, mice in the former condition showed reduced fear responses in an auditory fear conditioning test, compared with mice in the latter condition. In both electrophysiological and behavioral experiments, the effect of a diet with a high ω3 to ω6 PUFA diet ratio was completely blocked by treatment with a CB1 receptor antagonist. Furthermore, a significant reduction was observed in cholesterol content, but not in the level of an endogenous CB1 receptor agonist, 2-arachidonoylglycerol (2-AG), in brain samples containing the amygdala. These results suggest that the balance of ω3 to ω6 PUFA has an impact on fear memory and cortico-amygdala synaptic plasticity, both in a CB1 receptor–dependent manner. PMID:27601985

  8. Temporal Variation in Honey Production by the Stingless Bee Melipona subnitida (Hymenoptera: Apidae): Long-Term Management Reveals its Potential as a Commercial Species in Northeastern Brazil.

    PubMed

    Koffler, Sheina; Menezes, Cristiano; Menezes, Paulo Roberto; Kleinert, Astrid de Matos Peixoto; Imperatriz-Fonseca, Vera Lucia; Pope, Nathaniel; Jaffé, Rodolfo

    2015-06-01

    Even though stingless beekeeping has a great potential as a sustainable development tool, the activity remains essentially informal, technical knowledge is scarce, and management practices lack the sophistication and standardization found in apiculture. Here, we contributed to the further development of stingless beekeeping by investigating the long-term impact of management and climate on honey production and colony survival in the stingless bee Melipona subnitida Ducke (1910). We analyzed a 10-yr record of 155 M. subnitida colonies kept by a commercial honey producer of northeastern Brazil. This constitutes the longest and most accurate record available for a stingless bee. We modeled honey production in relation to time (years), age, management practices (colony division and food supplementation), and climatic factors (temperature and precipitation), and used a model selection approach to identify which factors best explained honey production. We also modeled colony mortality in relation to climatic factors. Although the amount of honey produced by each colony decreased over time, we found that the probability of producing honey increased over the years. Colony divisions decreased honey production, but did not affect honey presence, while supplementary feeding positively affected honey production. In warmer years, the probability of producing honey decreased and the amount of honey produced was lower. In years with lower precipitation, fewer colonies produced honey. In contrast, colony mortality was not affected by climatic factors, and some colonies lived up to nine years, enduring extreme climatic conditions. Our findings provide useful guidelines to improve management and honey production in stingless bees.

  9. The Role of Brain-Derived Neurotrophic Factor Receptors in the Mature Hippocampus: Modulation of Long-Term Potentiation through a Presynaptic Mechanism involving TrkB

    PubMed Central

    Xu, Baoji; Gottschalk, Wolfram; Chow, Ana; Wilson, Rachel I.; Schnell, Eric; Zang, Keling; Wang, Denan; Nicoll, Roger A.; Lu, Bai; Reichardt, Louis F.

    2009-01-01

    The neurotrophin BDNF has been shown to modulate long-term potentiation (LTP) at Schaffer collateral-CA1 hippocampal synapses. Mutants in the BDNF receptor gene trkB and antibodies to its second receptor p75NTR have been used to determine the receptors and cells involved in this response. Inhibition of p75NTR does not detectably reduce LTP or affect presynaptic function, but analyses of newly generated trkB mutants implicate TrkB. One mutant has reduced expression in a normal pattern of TrkB throughout the brain. The second mutant was created by cre-loxP-mediated removal of TrkB in CA1 pyramidal neurons of this mouse. Neither mutant detectably impacts survival or morphology of hippocampal neurons. TrkB reduction, however, affects presynaptic function and reduces the ability of tetanic stimulation to induce LTP. Postsynaptic glutamate receptors are not affected by TrkB reduction, indicating that BDNF does not modulate plasticity through postsynaptic TrkB. Consistent with this, elimination of TrkB in postsynaptic neurons does not affect LTP. Moreover, normal LTP is generated in the mutant with reduced TrkB by a depolarization–low-frequency stimulation pairing protocol that puts minimal demands on presynaptic terminal function. Thus, BDNF appears to act through TrkB presynaptically, but not postsynaptically, to modulate LTP. PMID:10995833

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

    PubMed

    Vazquez, Enrique; Barranco, Alejandro; Ramirez, Maria; Gruart, Agnes; Delgado-Garcia, Jose M; Jimenez, Maria L; Buck, Rachael; Rueda, Ricardo

    2016-01-01

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

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

    SciTech Connect

    Wu Chuanyun; Liu Bing; Wang Huili; Ruan Diyun

    2011-10-15

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

  12. Evalution of Renal Involvement in Patients with Behçet Disease: Need to be Aware About Potential Hypertension in Long Term Follow Up?

    PubMed Central

    Ozel, Deniz; Ozel, Betul Duran; Ozkan, Fuat; Kutlu, Ramazan

    2016-01-01

    Summary Backround The aim of this study was to evaluate frequency and severity of kidney involvement with some clinical, ultrasonography and color Doppler measurements in patients with Behçet disease. Material/Methods This study was including 32 patients with Behçet disease and 32 healthy sex and age-matched control subjects. Patients were divided into two groups as period of disease 0–6 years and 7 years and above to evaluate effect of duration of disease. We evaluated some biochemical tests in both blood and urine related to renal functions, blood pressure values. Gray scale and color Doppler findings were noted. Results Renal artery volume flow in patients with a duration of 7 years or above was significantly decreased compared to control group (p<0.05). However, gray scale ultrasound and color Doppler measurements reveal there was not statistically significant change compared to control group. There was no biochemical abnormalities in any patient. Four patients had elevated blood pressure but mean blood pressure values were not statistically different compared to volunteers. Conclusions Renal involvement ratios varies in different studies but not common. End stage renal failure can be seen very rare. Furthermore, vasculitic changes can lead renal artery narrowness and can result to decrease in renal blood flow. It has a potential to activate renin angiotensin aldosterone cascade to elevate blood pressure. We must be aware about blood pressure of patients with Behçet disease, especially with long term follow up. PMID:26937259

  13. Global aerosol retrieval by synergistic use of ESA ENVISAT instruments and potential for long-term aerosol records from Sentinel-3

    NASA Astrophysics Data System (ADS)

    North, P. R.; Bevan, S. L.; Brockmann, C.; Fischer, J.; Gomez-Chova, L.; Grey, W.; Heckel, A.; Moreno, J. F.; Munoz Mari, J.; Preusker, R.; Regner, P.

    2009-12-01

    We present research on for improved global aerosol retrieval by synergistic use of optical sensors on the European Space Agency ENVISAT satellite, MERIS and AATSR. Previously aerosol retrievals have been developed in isolation for these instruments, using spectral and mult-angular approaches respectively. These sensors will be succeeded with improved specification on the Sentinel-3 mission (2012-2030) with the aim to offer data suitable for long-term climate records. The research aims to use combined multi-angular and spectral approaches to constrain the inverse problem. The MERIS and AATSR instruments onboard ENVISAT provide similar resolution and swath but complementary information, encompassing different spectral domains and viewing geometries. Substantial success has been obtained previously by a number of researchers in using the instruments independently; for example MERIS aerosol retrieval using spectral methods over known targets, and AATSR approaches using the dual-view capability. The research explores the gain by using information from both instruments simultaneously to constrain atmospheric profile, characterise cloud, and provide improved atmospheric correction to surface reflectance. Results suggest improved estimation of aerosol properties compared to single-instrument retrievals, when compared with AERONET. A sensitivity study is performed to evaluate potential of Sentinel-3 for aerosol retreval, to be launched in 2012, which will give continuity with enhanced instrument specifications for the successor instruments OLCI and SLSTR.

  14. Effects of individual segmental trisomies of human chromosome 21 syntenic regions on hippocampal long-term potentiation and cognitive behaviors in mice

    PubMed Central

    Yu, Tao; Liu, Chunhong; Belichenko, Pavel; Clapcote, Steven J.; Li, Shaomin; Pao, Annie; Kleschevnikov, Alexander; Bechard, Allison R.; Asrar, Suhail; Chen, Rongqing; Fan, Ni; Zhou, Zhenyu; Jia, Zhengping; Chen, Chu; Roder, John C.; Liu, Bin; Baldini, Antonio; Mobley, William C.; Yu, Y. Eugene

    2010-01-01

    As the genomic basis for Down syndrome (DS), human trisomy 21 is the most common genetic cause of intellectual disability in children and young people. The genomic regions on human chromosome 21 (Hsa21) are syntenic to three regions in the mouse genome, located on mouse chromosome 10 (Mmu10), Mmu16 and Mmu17. Recently, we have developed three new mouse models using chromosome engineering carrying the genotypes of Dp(10)1Yey/+, Dp(16)1Yey/+, or Dp(17)1Yey/+, which harbor a duplication spanning the entire Hsa21 syntenic region on Mmu10, Mmu16, or Mmu17, respectively. In this study, we analyzed the hippocampal long-term potentiation (LTP) and cognitive behaviors of these models. Our results show that, while the genotype of Dp(17)1Yey/+ results in abnormal hippocampal LTP, the genotype of Dp(16)1Yey/+ leads to both abnormal hippocampal LTP and impaired learning/memory. Therefore, these mutant mice can serve as powerful tools for further understanding the mechanism underlying cognitively relevant phenotypes associated with DS, particularly the impacts of different syntenic regions on these phenotypes. PMID:20932954

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

    PubMed

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

    2016-03-01

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

  16. Quantitative analysis of long-term potentiation in the hippocampal dentate gyrus of the freely-moving 15-day-old rat.

    PubMed

    Bronzino, J D; Abu-Hasaballah, K; Austin-LaFrance, R J; Morgane, P J

    1995-01-01

    The magnitude and duration of long-term potentiation (LTP) of perforant path/dentate granule cell synapses was examined in freely moving rats beginning at 15 days of age. Measures of dentate granule cell population EPSP slope and population spike amplitude (PSA) obtained before and after tetanization were used to evaluate the level of LTP. Tetanization resulted in significant enhancement of both the population EPSP slope (approximately +75%) and PSA (approximately +40%) measures. This enhancement was maintained without significant change for 18 h, after which both measures began a steady and continuous rise. Daily input/output response measures from age-matched nontetanized animals were used to factor out enhancement related to normal development. Under this schema, tetanization-induced enhancement of both EPSP slope and PSA measures decayed slowly, beginning 18-24 h after tetanization, returning to baseline 5 days after tetanization. Enhancement obtained from 90-day-old animals decayed to baseline 24 h after tetanization. The longer duration of LTP obtained from preweanlings is discussed with regard to the development of inhibitory systems modulating granule cell excitability.

  17. Pilocarpine-Induced Status Epilepticus Is Associated with Changes in the Actin-Modulating Protein Synaptopodin and Alterations in Long-Term Potentiation in the Mouse Hippocampus

    PubMed Central

    Lenz, Maximilian; Ben Shimon, Marina; Deller, Thomas

    2017-01-01

    Epilepsy is a complex neurological disorder which can severely affect neuronal function. Some patients may experience status epilepticus, a life-threatening state of ongoing seizure activity associated with postictal cognitive dysfunction. However, the molecular mechanisms by which status epilepticus influences brain function beyond seizure activity remain not well understood. Here, we addressed the question of whether pilocarpine-induced status epilepticus affects synaptopodin (SP), an actin-binding protein, which regulates the ability of neurons to express synaptic plasticity. This makes SP an interesting marker for epilepsy-associated alterations in synaptic function. Indeed, single dose intraperitoneal pilocarpine injection (250 mg/kg) in three-month-old male C57BL/6J mice leads to a rapid reduction in hippocampal SP-cluster sizes and numbers (in CA1 stratum radiatum of the dorsal hippocampus; 90 min after injection). In line with this observation (and previous work using SP-deficient mice), a defect in the ability to induce long-term potentiation (LTP) of Schaffer collateral-CA1 synapses is observed. Based on these findings we propose that status epilepticus could exert its aftereffects on cognition at least in part by perturbing SP-dependent mechanisms of synaptic plasticity. PMID:28154762

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

    PubMed

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

    2016-05-01

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

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

    PubMed Central

    Vazquez, Enrique; Barranco, Alejandro; Ramirez, Maria; Gruart, Agnes; Delgado-Garcia, Jose M.; Jimenez, Maria L.; Buck, Rachael; Rueda, Ricardo

    2016-01-01

    2´-fucosyllactose (2´-FL) is an abundant human milk oligosaccharide (HMO) in human milk with diverse biological effects. We recently reported ingested 2´-FL stimulates central nervous system (CNS) function, such as hippocampal long term potentiation (LTP) and learning and memory in rats. Conceivably the effect of 2´-FL on CNS function may be via the gut-brain axis (GBA), specifically the vagus nerve, and L-fucose (Fuc) may play a role. This study had two aims: (1) determine if the effect of ingested 2´-FL on the modulation of CNS function is dependent on the integrity of the molecule; and (2) confirm if oral 2´-FL modified hippocampal LTP and associative learning related skills in rats submitted to bilateral subdiaphragmatic vagotomy. Results showed that 2´-FL but not Fuc enhanced LTP, and vagotomy inhibited the effects of oral 2´-FL on LTP and associative learning related paradigms. Taken together, the data show that dietary 2´-FL but not its Fuc moiety affects cognitive domains and improves learning and memory in rats. This effect is dependent on vagus nerve integrity, suggesting GBA plays a role in 2´-FL-mediated cognitive benefits. PMID:27851789

  20. Prestorage oxalic acid treatment maintained visual quality, bioactive compounds, and antioxidant potential of pomegranate after long-term storage at 2 degrees C.

    PubMed

    Sayyari, Mohammad; Valero, Daniel; Babalar, Mesbah; Kalantari, Siamak; Zapata, Pedro J; Serrano, María

    2010-06-09

    Oxalic acid at three concentrations (2, 4, and 6 mM) was applied by dipping to pomegranate fruits of cv. Mollar de Elche, which were then stored for 84 days at 2 degrees C. Pomegranate is a chilling-sensitive fruit and, thus, control fruits exhibited chilling injury (CI) symptoms after long-term storage at 2 degrees C that were accompanied by increased respiration rate, weight loss, and electrolyte leakage (EL). The CI symptoms were significantly reduced by oxalic acid treatment, especially for the 6 mM concentration. In addition, control pomegranates showed significant reduction in the content of total phenolics and ascorbic acid as well as in total antioxidant activity (TAA), in both hydrophilic (H-TAA) and lipophilic (L-TAA) fractions. The application of oxalic acid led to lower losses of total phenolics and significant increase in both ascorbic acid content and H-TAA, whereas L-TAA remained unaffected. Thus, oxalic acid could be a promising postharvest treatment to alleviate CI and increase antioxidant potential.

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

    PubMed

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

    2017-03-15

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

  2. Methodological Aspects of the Potential Use of Dendrochronological Techniques When Analyzing the Long-Term Impact of Tourism on Protected Areas

    PubMed Central

    Ciapała, Szymon; Adamski, Paweł

    2015-01-01

    Intensification of pedestrian tourism causes damage to trees near tourist tracks, and likewise changes the soil structure. As a result, one may expect that annual amount of trees growing near tracks is significantly lower than deeper in the forest. However, during the study of the long-term impact of tourism on the environment (determined from tree increment dynamics), some methodological problems may occur. It is particularly important in protected areas where law and administrative regulations related to nature conservation force research to be conducted using small samples. In this paper we have analyzed the data collected in the Polish part of the Tatra National Park in the two study plots divided into two zones each: the area directly under the influence of the tourist's trampling and the control group. The aim of such analyses was to present the potential effects of the factors which may affect the results of dendrochronological analysis: (i) small size of samples that affects their representativeness, (ii) spatial differences in the rates of the process, as a result of spatial variability of environmental factors and (iii) temporal differences in the rates of the process. This study confirms that the factors mentioned above could significantly influence the results and should be taken into consideration during the analysis. PMID:26325062

  3. TRPA1 Channels Are Regulators of Astrocyte Basal Calcium Levels and Long-Term Potentiation via Constitutive d-Serine Release

    PubMed Central

    Shigetomi, Eiji; Jackson-Weaver, Olan; Huckstepp, Robert T.

    2013-01-01

    Astrocytes are found throughout the brain where they make extensive contacts with neurons and synapses. Astrocytes are known to display intracellular Ca2+ signals and release signaling molecules such as d-serine into the extracellular space. However, the role(s) of astrocyte Ca2+ signals in hippocampal long-term potentiation (LTP), a form of synaptic plasticity involved in learning and memory, remains unclear. Here, we explored a recently discovered novel TRPA1 channel-mediated transmembrane Ca2+ flux pathway in astrocytes. Specifically, we determined whether block or genetic deletion of TRPA1 channels affected LTP of Schaffer collateral to CA1 pyramidal neuron synapses. Using pharmacology, TRPA1−/− mice, imaging, electrophysiology, and d-serine biosensors, our data indicate that astrocyte TRPA1 channels contribute to basal Ca2+ levels and are required for constitutive d-serine release into the extracellular space, which contributes to NMDA receptor-dependent LTP. The findings have broad relevance for the study of astrocyte–neuron interactions by demonstrating how TRPA1 channel-mediated fluxes contribute to astrocyte basal Ca2+ levels and neuronal function via constitutive d-serine release. PMID:23761909

  4. Developmental exposure to a commercial PCB mixture (Aroclor 1254) produces a persistent impairment in long-term potentiation in the rat dentate gyrus in vivo.

    PubMed

    Gilbert, M E; Crofton, K M

    1999-12-11

    Developmental exposure to polycholorinated biphenyls (PCBs) has been associated with cognitive deficits in humans and laboratory animals. The present study sought to examine synaptic plasticity in the hippocampus, a brain region critical for some types of memory function, in animals exposed to PCBs early in development. Pregnant Long-Evans rats were administered either corn oil (control) or 6 mg/kg/day of a commercial PCB mixture, Aroclor 1254 (A1254) by gavage from gestational day (GD) 6 until pups were weaned on postnatal day (PND) 21. In adult male offspring (3-6 months of age), field potentials evoked by perforant path stimulation were recorded in the dentate gyrus under urethane anesthesia. Input/output (I/O) functions were assessed by averaging the response evoked in the dentate gyrus to stimulus pulses delivered to the perforant path in an ascending intensity series. Long-term potentiation (LTP) was induced by delivering a series of brief high frequency (400 Hz) train bursts to the perforant path at a moderate stimulus intensity and I/O functions were reassessed 1 h later. No differences in baseline synaptic population spike (PS) and minor effects on excitatory postsynaptic potential (EPSP) slope amplitudes were discerned between the groups prior to train delivery. Post-train I/O functions, however, revealed a 50% decrement in the magnitude of LTP in PCB-exposed animals. These data are the first to demonstrate persistent decrements in hippocampal synaptic plasticity in the intact animal following developmental exposure to PCBs. Disruption of early brain ontogeny due to developmental PCB exposure may underlie perturbations in the neurological substrates that support synaptic plasticity and contribute to deficits in LTP and learning that persist into adulthood.

  5. Age-Dependent Switch of the Role of Serotonergic 5-HT1A Receptors in Gating Long-Term Potentiation in Rat Visual Cortex In Vivo

    PubMed Central

    Gagolewicz, Peter J.; Dringenberg, Hans C.

    2016-01-01

    The rodent primary visual cortex (V1) is densely innervated by serotonergic axons and previous in vitro work has shown that serotonin (5-HT) can modulate plasticity (e.g., long-term potentiation (LTP)) at V1 synapses. However, little work has examined the effects of 5-HT on LTP under in vivo conditions. We examined the role of 5-HT on LTP in V1 elicited by theta burst stimulation (TBS) of the lateral geniculate nucleus in urethane-anesthetized (adult and juvenile) rats. Thalamic TBS consistently induced potentiation of field postsynaptic potentials (fPSPs) recorded in V1. While 5-HT application (0.1–10 mM) itself did not alter LTP levels, the broad-acting 5-HT receptor antagonists methiothepin (1 mM) resulted in a clear facilitation of LTP in adult animals, an effect that was mimicked by the selective 5-HT1A receptor antagonist WAY 100635 (1 mM). Interestingly, in juvenile rats, WAY 100635 application inhibited LTP, indicative of an age-dependent switch in the role of 5-HT1A receptors in gating V1 plasticity. Analyses of spontaneous electrocorticographic (ECoG) activity in V1 indicated that the antagonist-induced LTP enhancement was not related to systematic changes in oscillatory activity in V1. Together, these data suggest a facilitating role of 5-HT1A receptor activation on LTP in the juvenile V1, which switches to a tonic, inhibitory influence in adulthood. PMID:27247804

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

    PubMed

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

    2013-09-01

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

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

    SciTech Connect

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

    2013-09-01

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

  8. A novel β-sheet breaker, RS-0406, reverses amyloid β-induced cytotoxicity and impairment of long-term potentiation in vitro

    PubMed Central

    Nakagami, Yasuhiro; Nishimura, Satoko; Murasugi, Takako; Kaneko, Isao; Meguro, Masaki; Marumoto, Shinji; Kogen, Hiroshi; Koyama, Kazuo; Oda, Tomiichiro

    2002-01-01

    Fibril formation of amyloid β peptide (Aβ) is considered to be responsible for the pathology of Alzheimer's disease (AD). The Aβ fibril is formed by a protein misfolding process in which intermolecular β-sheet interactions become stabilized abnormally. Thus, to develop potential anti-AD drugs, we screened an in-house library to find compounds which have a profile as a β-sheet breaker. We searched for a β-sheet breaker profile in an in-house library of approximately 113,000 compounds. From among the screening hits, we focused on N,N′-bis(3-hydroxyphenyl)pyridazine-3,6-diamine (named RS-0406), which had been newly synthesized in our laboratory. This compound (10–100 μg ml−1) was found to be capable of significantly inhibiting 25 μM Aβ1–42 fibrillogenesis and, furthermore, disassembling preformed Aβ1–42 fibrils in vitro. We then investigated the effect of RS-0406 on 111 nM Aβ1–42-induced cytotoxicity in primary hippocampal neurons, and found that 0.3–3 μg ml−1 RS-0406 ameliorates the cytotoxicity. Moreover, 3 μg ml−1 RS-0406 reversed 1 μM Aβ1–42-induced impairment of long-term potentiation in hippocampal slices. In this study, we have succeeded in identifying RS-0406 which has potential to inhibit Aβ1–42 fibrillogenesis, and to protect neurons against Aβ1–42-induced biological toxicity in vitro. These results suggest that RS-0406 or one of the derivatives could become a therapeutic agent for AD patients. PMID:12381681

  9. Acetyl-L-carnitine normalizes the impaired long-term potentiation and spine density in a rat model of global ischemia.

    PubMed

    Kocsis, K; Knapp, L; Gellért, L; Oláh, G; Kis, Zs; Takakuwa, H; Iwamori, N; Ono, E; Toldi, J; Farkas, T

    2014-06-06

    As a consequence of an ischemic episode, energy production is disturbed, leading to neuronal cell death. Despite intensive research, the quest for promising neuroprotective drugs has largely failed, not only because of ineffectiveness, but also because of serious side-effects and dosing difficulties. Acetyl-l-carnitine (ALC) is an essential nutrient which plays a key role in energy metabolism by transporting fatty acids into mitochondria for β-oxidation. It is an endogenous compound and can be used at high dose without toxicity in research into ischemia. Its neuroprotective properties have been reported in many studies, but its potential action on long-term potentiation (LTP) and dendritic spine density has not been described to date. The aim of the present study was an evaluation of the possible protective effect of ALC after ischemic insults inflicted on hippocampal synaptic plasticity in a 2-vessel occlusion (2VO) model in rats. For electrophysiological measurements, LTP was tested on hippocampal slices. The Golgi-Cox staining technique was used to determine spine density. 2VO resulted in a decreased, unstable LTP and a significant loss of dendritic spines. ALC administered after 2VO was not protective, but as pretreatment prior to 2VO it restored LTP nearly to the control level. This finding paralleled the histological analysis: ALC pretreatment resulted in the reappearance of dendritic spines on the CA1 pyramidal cells. Our data demonstrate that ALC administration can restore hippocampal function and spine density. ALC probably acts by enhancing the aerobic metabolic pathway, which is inhibited during and following ischemic attacks.

  10. IN VIVO EVALUATION OF SKIN IRRITATION POTENTIAL, MELASMA AND SEBUM CONTENT FOLLOWING LONG TERM APPLICATION OF SKIN CARE CREAM IN HEALTHY ADULTS, USING NON-INVASIVE BIOMETROLOGICAL TECHNIQUES.

    PubMed

    Arshad, Atif I; Khan, Shoaib H M; Akhtar, Naveed; Mahmood, Asif; Sarfraz, Rai Muhammad

    2016-01-01

    The present investigation was conducted to evaluate non-invasively, various functional skin parameters i.e., irritation potential, melasma and sebum contents following long term application of topical cream (w/o) loaded with 2% methanolic extract of Ananas comosus L. versus placebo control (base) in healthy adults. Healthy human volunteers (n = 11, aged 20-30 years) were recruited for investigation and written informed consent was taken from each volunteer. In this single blinded study every volunteer applied formulation on one side of face and placebo on the other side of face twice daily for a period of 12 weeks (three months). Different skin parameters i.e., skin irritancy, melasma, and sebum contents were measured on both sides of face at baseline and after two weeks interval, using photometric device Mexameter and Sebumeter in a draught free room with modulated conditions of temperature (22-25°C) and humidity (55-60%). It was evident from the results that no primary skin irritancy was observed with patch test. Besides, statistical interpretation indicates that treatment with formulation is superior to placebo because it significantly (p ≤ 0.05) reduced the skin irritancy, melasma and sebum secretions throughout the study and reaching maximum -20.76 ± 0.89, -54.2 ± 0.37 and -40.71 ± 0.75%, respectively, at the end of study period. Antioxidant activity of extract was 92% compared to standard antioxidant. Conclusively, active cream loaded with fruit extract was well tolerated by all the volunteers and suitable to treat contact dermatitis, greasy skin, acne and seborrheic dermatitis and augmenting beauty and attraction by depigmentation of human skin. So, in the future, there is need to clinically evaluate these formulations in patients with compromised skin functions i.e., contact dermatitis, melasma, and acne vulgaris in order to explore the actual potential of this fruit.

  11. Allosteric Modulation of Related Ligand-Gated Ion Channels Synergistically Induces Long-Term Potentiation in the Hippocampus and Enhances Cognition

    PubMed Central

    Gu, Zhenglin; Yoshimura, Ryan F.; Villegier, Anne-Sophie; Hogenkamp, Derk J.; Whittemore, Edward R.; Huang, Jin-Cheng; Tran, Minhtam B.; Belluzzi, James D.; Yakel, Jerrel L.; Gee, Kelvin W.

    2011-01-01

    α5 Subunit-containing GABAA receptors (GABAARs) and α7 neuronal nicotinic-acetylcholine receptors (nAChRs) are members of the Cys-loop family of ligand-gated ion channels (LGICs) that mediate cognitive and attentional processes in the hippocampus. α5 GABAARs alter network activity by tonic inhibition of CA1/CA3 pyramidal cells of the hippocampus. Postsynaptic α7 nAChRs in the hippocampus regulate inhibitory GABAergic interneuron activity required for synchronization of pyramidal neurons in the CA1, whereas presynaptic α7 nAChRs regulate glutamate release. Can simultaneous allosteric modulation of these LGICs produce synergistic effects on cognition? We show that combined transient application of two allosteric modulators that individually 1) inhibit α5 GABAARs and 2) enhance α7 nAChRs causes long-term potentiation (LTP) of mossy fiber stimulation-induced excitatory postsynaptic currents (EPSC) from CA1 pyramidal neurons of rat hippocampal slices. The LTP effect evoked by two compounds is replicated by 3-(2,5-difluorophenyl)-6-(N-ethylindol-5-yl)-1,2,4-triazolo[4,3-b]pyridazine (522-054), a compound we designed to simultaneously inhibit α5 GABAARs and enhance α7 nAChRs. Selective antagonists for either receptor block sustained EPSC potentiation produced by 522-054. In vivo, 522-054 enhances performance in the radial arm maze and facilitates attentional states in the five-choice serial reaction time trial with similar receptor antagonist sensitivity. These observations may translate into therapeutic utility of dual action compounds in diseases of hippocampal-based cognitive impairment. PMID:21159751

  12. Loss of α1,6-Fucosyltransferase Decreases Hippocampal Long Term Potentiation: IMPLICATIONS FOR CORE FUCOSYLATION IN THE REGULATION OF AMPA RECEPTOR HETEROMERIZATION AND CELLULAR SIGNALING.

    PubMed

    Gu, Wei; Fukuda, Tomohiko; Isaji, Tomoya; Hang, Qinglei; Lee, Ho-hsun; Sakai, Seiichiro; Morise, Jyoji; Mitoma, Junya; Higashi, Hideyoshi; Taniguchi, Naoyuki; Yawo, Hiromu; Oka, Shogo; Gu, Jianguo

    2015-07-10

    Core fucosylation is catalyzed by α1,6-fucosyltransferase (FUT8), which transfers a fucose residue to the innermost GlcNAc residue via α1,6-linkage on N-glycans in mammals. We previously reported that Fut8-knock-out (Fut8(-/-)) mice showed a schizophrenia-like phenotype and a decrease in working memory. To understand the underlying molecular mechanism, we analyzed early form long term potentiation (E-LTP), which is closely related to learning and memory in the hippocampus. The scale of E-LTP induced by high frequency stimulation was significantly decreased in Fut8(-/-) mice. Tetraethylammonium-induced LTP showed no significant differences, suggesting that the decline in E-LTP was caused by postsynaptic events. Unexpectedly, the phosphorylation levels of calcium/calmodulin-dependent protein kinase II (CaMKII), an important mediator of learning and memory in postsynapses, were greatly increased in Fut8(-/-) mice. The expression levels of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors (AMPARs) in the postsynaptic density were enhanced in Fut8(-/-) mice, although there were no significant differences in the total expression levels, implicating that AMPARs without core fucosylation might exist in an active state. The activation of AMPARs was further confirmed by Fura-2 calcium imaging using primary cultured neurons. Taken together, loss of core fucosylation on AMPARs enhanced their heteromerization, which increase sensitivity for postsynaptic depolarization and persistently activate N-methyl-d-aspartate receptors as well as Ca(2+) influx and CaMKII and then impair LTP.

  13. Long-term reindeer grazing limits warming-induced increases in CO2 released by tundra heath soil: potential role of soil C quality

    NASA Astrophysics Data System (ADS)

    Väisänen, Maria; Sjögersten, Sofie; Large, David; Drage, Trevor; Stark, Sari

    2015-09-01

    The current climate warming in the Arctic may increase the microbial degradation of vast pools of soil carbon (C); however, the temperature sensitivity of decomposition is often highly dependent on the quality of accumulated soil C. Grazing by reindeer (Rangifer tarandus L.) substantially affects the dominant vegetation and often increases graminoids in relation to dwarf shrubs in ecosystems, but the effect of this vegetation shift on the soil C quality has not been previously investigated. We analyzed the soil C quality and rate of microbially mediated CO2 release at different temperatures in long-term laboratory incubations using soils from lightly grazed dwarf shrub-dominated and heavily grazed graminoid-dominated tundra ecosystem. The soil C quality was characterized by solid-state cross-polarization magic angle spinning (CPMAS 13C NMR) spectroscopy, which showed a higher relative proportion of carbohydrate C under light grazing and higher relative proportion of aliphatic not-O-substituted C under heavy grazing. Initial measurements showed lower temperature sensitivity of the CO2 release in soils under light grazing compared with soil under heavy grazing, but the overall CO2 release rate and its temperature sensitivity increased under light grazing as the soil incubation progressed. At the end of incubation, significantly more carbohydrate C had been lost in soils under light grazing compared with heavy grazing. These findings indicate that there may be a link between the grazer-induced effects on soil C quality and the potential of soils to release CO2 to atmosphere. We suggest that vegetation shifts induced by grazing could influence the proportion of accumulated soil C that is vulnerable to microbial degradation under warming climate.

  14. Oxidative Impairment of Hippocampal Long-term Potentiation Involves Activation of Protein Phosphatase 2A and Is Prevented by Ketone Bodies

    PubMed Central

    Maalouf, Marwan; Rho, Jong M.

    2008-01-01

    Previous studies have shown that ketone bodies (KB) exert antioxidant effects in experimental models of neurological disease. In the present study, we explored the effects of the KB acetoacetate (ACA) and β-hydroxybutyrate (BHB) on impairment of hippocampal long-term potentiation (LTP) in rats by hydrogen peroxide (H2O2) using electrophysiological, fluorescence imaging and enzyme assay techniques. We found that: (1) a combination of ACA and BHB (1 mM each) prevented impairment of LTP by H2O2 (200 μM); (2) KB significantly lowered intracellular levels of reactive oxygen species (ROS) — measured with the fluorescent indicator carboxy-H2DCFDA — in CA1 pyramidal neurons exposed to H2O2; (3) the effect of KB on LTP was replicated by the protein phosphatase 2A (PP2A) inhibitor fostriecin; (4) KB prevented impairment of LTP by the PP2A activator C6 ceramide; (5) fostriecin did not prevent the increase in ROS levels in CA1 pyramidal neurons exposed to H2O2, and C6 ceramide did not increase ROS levels; (6) PP2A activity was enhanced by both H2O2and rotenone – a mitochondrial complex I inhibitor that increases endogenous superoxide production; and (7) KB inhibited PP2A activity in protein extracts from brain tissue treated with either H2O2 or ceramide. We propose that oxidative impairment of hippocampal LTP is associated with PP2A activation, and that KB prevent this impairment in part by inducing PP2A inhibition through an antioxidant mechanism. PMID:18646208

  15. Venlafaxine treatment stimulates expression of brain-derived neurotrophic factor protein in frontal cortex and inhibits long-term potentiation in hippocampus.

    PubMed

    Cooke, J D; Grover, L M; Spangler, P R

    2009-09-15

    Antidepressant action may involve stimulation of brain-derived neurotrophic factor (BDNF). BDNF also regulates long-term potentiation (LTP). We hypothesized that the 5-HT and norepinephrine reuptake inhibitor, venlafaxine, would stimulate BDNF expression and alter LTP more effectively than the selective 5-HT reuptake inhibitor, citalopram. To test this, we administered venlafaxine or citalopram to rats for 1 or 3 weeks; control rats received vehicle only. We measured BDNF protein in hippocampal and frontal cortex homogenates, and serum. We assessed LTP in area cornu ammonis region 1 (CA1) of in vitro hippocampal brain slices. We also examined input/output function to determine if basal synaptic transmission in area CA1 was altered. Compared to vehicle control, frontal cortex BDNF protein was significantly greater after three, but not one, weeks of venlafaxine treatment. In contrast, citalopram (1 or 3 weeks) did not stimulate BDNF. The stimulatory effect of venlafaxine treatment on BDNF was superimposed on a general time-dependent decrease in expression which was seen in both vehicle control and citalopram-treated animals. LTP was significantly impaired in slices from venlafaxine-treated rats after both 1 and 3 weeks of treatment, but LTP appeared normal in slices from citalopram-treated and vehicle control rats. The LTP impairment caused by venlafaxine treatment was independent of changes in BDNF: LTP was impaired after only 1 week of treatment, prior to any effect on BDNF, and LTP magnitude was not correlated with BDNF protein concentration. Input/output function was significantly but equally reduced after 3 weeks of citalopram, venlafaxine, or control treatment. Decreased BDNF protein in citalopram and vehicle control animals, and decreased input/output function may be consequences of individual housing of animals, which we used to ensure proper dosing. Venlafaxine stimulation of BDNF and inhibition of LTP may be related to the reported effectiveness of

  16. Investigating the potential for long-term permeable reactive barrier (PRB) monitoring from the electrical signatures associated with the reduction in reactive iron performance

    SciTech Connect

    Slater, Lee D.; Korte, N.; Baker, J.

    2005-12-14

    The objective of this work was to conduct laboratory and field experiments to determine the sensitivity of low frequency electrical measurements (resistivity and induced polarization) to the processes of corrosion and precipitation that are believed to limit permeable reactive barrier (PRB) performance. The research was divided into four sets of experiments that were each written up and submitted to a peer-reviewed journal: [1] A laboratory experiment to define the controls of aqueous chemistry (electrolyte activity; pH; valence) and total zero valent iron (Fe0) available surface area on the electrical properties of Fe0 columns. [2] A laboratory experiment to determine the impact of corrosion and precipitation on the electrical response of synthetic Fe0 columns as a result of geochemical reactions with NaSO4 and NaCO3 electrolytes. [3] Laboratory experiments on a sequence of cores retrieved from the Kansas City PRB to determine the magnitude of electrical and geochemical changes within a field active PRB after eight years of operation [4] Field-scale cross borehole resistivity and induced polarization monitoring of the Kansas City PRB to evaluate the potential of electrical imaging as a technology for non-invasive, long-term monitoring of indicators of reduced PRB performance This report first summarizes the findings of the four major experiments conducted under this research. The reader is referred to the four papers in Appendices 1-4 for a full description of each experiment, including motivation and significance, technical details, findings and implications. The deliverables of the project, including the publications, conference papers and new collaborative arrangements that have resulted are then described. Appendices 5-6 contain two technical reports written by co-PI Korte describing (1) supporting geochemical measurements, and (2) the coring procedure, conducted at the Kansas City PRB as part of this project.

  17. Functional basis of associative learning and its relationships with long-term potentiation evoked in the involved neural circuits: Lessons from studies in behaving mammals.

    PubMed

    Gruart, Agnès; Leal-Campanario, Rocío; López-Ramos, Juan Carlos; Delgado-García, José M

    2015-10-01

    While contemporary neuroscience is paying increasing attention to subcellular and molecular events and other intracellular phenomena underlying the acquisition, storage, and retrieval of newly acquired motor and cognitive abilities, parallel attention should be paid to the study of the electrophysiological phenomena taking place at selected cortical and subcortical neuronal and synaptic sites during the precise moment of learning acquisition, extinction, and recall. These in vivo approaches to the study of learning and memory processes will allow the proper integration of the important information collected from in vitro and delayed molecular studies. Here, we summarize studies in behaving mammals carried out in our laboratory during the past ten years on the relationships between experimentally evoked long-term potentiation (LTP) and activity-dependent changes in synaptic strength taking place in hippocampal, prefrontal and related cortical and subcortical circuits during the acquisition of classical eyeblink conditioning or operant learning tasks. These studies suggest that different hippocampal synapses are selectively modified in strength during the acquisition of classical, but not instrumental, learning tasks. In contrast, selected prefrontal and striatum synapses are more directly modified by operant conditioning. These studies also show that besides N-methyl-D-aspartate (NMDA) receptors, many other neurotransmitter, intracellular mediating, and transcription factors participate in these two types of associative learning. Although experimentally evoked LTP seems to prevent the acquisition of classical eyeblink conditioning when induced at selected hippocampal synapses, it proved to be ineffective in preventing the acquisition of operant conditioned tasks when induced at numerous hippocampal, prefrontal, and striatal sites. The differential roles of these cortical structures during these two types of associative learning are discussed, and a diagrammatic

  18. Enhancement of GluN2B Subunit-Containing NMDA Receptor Underlies Serotonergic Regulation of Long-Term Potentiation after Critical Period in the Rat Visual Cortex

    PubMed Central

    Joo, Kayoung; Rhie, Duck-Joo

    2015-01-01

    Serotonin [5-hydroxytryptamine (5-HT)] regulates synaptic plasticity in the visual cortex. Although the effects of 5-HT on plasticity showed huge diversity depending on the ages of animals and species, it has been unclear how 5-HT can show such diverse effects. In the rat visual cortex, 5-HT suppressed long-term potentiation (LTP) at 5 weeks but enhanced LTP at 8 weeks. We speculated that this difference may originate from differential regulation of neurotransmission by 5-HT between the age groups. Thus, we investigated the effects of 5-HT on apha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-, γ-aminobutyric acid receptor type A (GABAAR)-, and N-methyl-D-aspartic acid receptor (NMDAR)-mediated neurotransmissions and their involvement in the differential regulation of plasticity between 5 and 8 weeks. AMPAR-mediated currents were not affected by 5-HT at both 5 and 8 weeks. GABAAR-mediated currents were enhanced by 5-HT at both age groups. However, 5-HT enhanced NMDAR-mediated currents only at 8 weeks. The enhancement of NMDAR-mediated currents appeared to be mediated by the enhanced function of GluN2B subunit-containing NMDAR. The enhanced GABAAR- and NMDAR-mediated neurotransmissions were responsible for the suppression of LTP at 5 weeks and the facilitation of LTP at 8 weeks, respectively. These results indicate that the effects of 5-HT on neurotransmission change with development, and the changes may underlie the differential regulation of synaptic plasticity between different age groups. Thus, the developmental changes in 5-HT function should be carefully considered while investigating the 5-HT-mediated metaplastic control of the cortical network. PMID:26557019

  19. Test-Retest Reliability of 10 Hz Conditioning Electrical Stimulation Inducing Long-Term Potentiation (LTP)-Like Pain Amplification in Humans

    PubMed Central

    Xia, Weiwei; Mørch, Carsten Dahl; Andersen, Ole Kæseler

    2016-01-01

    Background 10 Hz conditioning electrical stimulation (CES) has been shown to induce long-term potentiation (LTP)-like pain amplification similar to traditional 100 Hz CES in healthy humans. The aim of this study was to assess the test-retest reliability and to estimate sample sizes required for future crossover and parallel study designs. Methods The 10 Hz paradigm (500 rectangular pulses lasting 50 s) was repeated on two separate days with one week interval in twenty volunteers. Perceptual intensities to single electrical stimulation (SES) at the conditioned skin site and to mechanical stimuli (pinprick and light stroking) in immediate vicinity to the conditioned skin site were recorded. Superficial blood flow (SBF) was assessed as indicator of neurogenic inflammation. All outcome measures were assessed with 10 min interval three times before and six times after the CES. The coefficient of variation and intra-class correlation coefficient were calculated within session and between sessions. Sample sizes were estimated for future crossover (Ncr) and parallel (Np) drug testing studies expected to detect a 30% decrease for the individual outcome measure following 10 Hz CES. Results Perceptual intensity ratings to light stroking (Ncr = 2, Np = 33) and pinprick stimulation (491 mN) (Ncr = 6, Np = 54) increased after CES and showed better reliability in crossover than parallel design. The SBF increased after CES, and then declined until reaching a plateau 20 minutes postCES. SBF showed acceptable reliability both in crossover and parallel designs (Ncr = 3, Np = 13). Pain ratings to SES were reliable, but with large estimated sample sizes (Ncr = 634, Np = 11310) due to the minor pain amplification. Conclusions The reliability of 10 Hz CES was acceptable in inducing LTP-like effects in the assessments of superficial blood flow, heterotopic mechanical hyperalgesia, and dysesthesia in terms of sample sizes for future crossover study designs. PMID:27529175

  20. Impaired Long-term Potentiation and Enhanced Neuronal Excitability in the Amygdala of CaV1.3 Knockout Mice

    PubMed Central

    McKinney, Brandon C.; Sze, Wilson; Lee, Benjamin; Murphy, Geoffrey G.

    2009-01-01

    Previously, we demonstrated that mice in which the gene for the L-type voltage-gated calcium channel CaV1.3 is deleted (CaV1.3 knockout mice) exhibit an impaired ability to consolidate contextually-conditioned fear. Given that this form of Pavlovian fear conditioning is critically dependent on the basolateral complex of the amygdala (BLA), we were interested in the mechanisms by which CaV1.3 contributes to BLA neurophysiology. In the present study, we used in vitro amygdala slices prepared from CaV1.3 knockout mice and wild-type littermates to explore the role of CaV1.3 in long-term potentiation (LTP) and intrinsic neuronal excitability in the BLA. We found that LTP in the lateral nucleus (LA) of the BLA, induced by high-frequency stimulation of the external capsule, was significantly reduced in CaV1.3 knockout mice. Additionally, we found that BLA principal neurons from CaV1.3 knockout mice were hyperexcitable, exhibiting significant increases in firing rates and decreased interspike intervals in response to prolonged somatic depolarization. This aberrant increase in neuronal excitability appears to be at least in part due to a concomitant reduction in the slow component of the post-burst afterhyperpolarization. Together, these results demonstrate altered neuronal function in the BLA of CaV1.3 knockout mice which may account for the impaired ability of these mice to consolidate contextually-conditioned fear. PMID:19595780

  1. The Contribution of Spatial and Temporal Molecular Networks in the Induction of Long-term Memory and Its Underlying Synaptic Plasticity

    PubMed Central

    Mirisis, Anastasios A.; Alexandrescu, Anamaria; Carew, Thomas J.; Kopec, Ashley M.

    2016-01-01

    The ability to form long-lasting memories is critical to survival and thus is highly conserved across the animal kingdom. By virtue of its complexity, this same ability is vulnerable to disruption by a wide variety of neuronal traumas and pathologies. To identify effective therapies with which to treat memory disorders, it is critical to have a clear understanding of the cellular and molecular mechanisms which subserve normal learning and memory. A significant challenge to achieving this level of understanding is posed by the wide range of distinct temporal and spatial profiles of molecular signaling induced by learning-related stimuli. In this review we propose that a useful framework within which to address this challenge is to view the molecular foundation of long-lasting plasticity as composed of unique spatial and temporal molecular networks that mediate signaling both within neurons (such as via kinase signaling) as well as between neurons (such as via growth factor signaling). We propose that evaluating how cells integrate and interpret these concurrent and interacting molecular networks has the potential to significantly advance our understanding of the mechanisms underlying learning and memory formation. PMID:27819030

  2. Long-term environmental stewardship.

    SciTech Connect

    Nagy, Michael David

    2010-08-01

    The purpose of this Supplemental Information Source Document is to effectively describe Long-Term Environmental Stewardship (LTES) at Sandia National Laboratories/New Mexico (SNL/NM). More specifically, this document describes the LTES and Long-Term Stewardship (LTS) Programs, distinguishes between the LTES and LTS Programs, and summarizes the current status of the Environmental Restoration (ER) Project.

  3. Long-term urethral catheterisation.

    PubMed

    Turner, Bruce; Dickens, Nicola

    This article discusses long-term urethral catheterisation, focusing on the relevant anatomy and physiology, indications for the procedure, catheter selection and catheter care. It is important that nurses have a good working knowledge of long-term catheterisation as the need for this intervention will increase with the rise in chronic health conditions and the ageing population.

  4. Milnacipran, a serotonin and noradrenaline reuptake inhibitor, suppresses long-term potentiation in the rat hippocampal CA1 field via 5-HT1A receptors and alpha 1-adrenoceptors.

    PubMed

    Tachibana, Kaori; Matsumoto, Machiko; Togashi, Hiroko; Kojima, Taku; Morimoto, Yuji; Kemmotsu, Osamu; Yoshioka, Mitsuhiro

    2004-03-04

    Pharmacological characteristics of a serotonin (5-HT) and noradrenaline reuptake inhibitor (SNRI), milnacipran, in modulation of the synaptic plasticity were investigated. Milnacipran (30 mg/kg, i.p.) suppressed the long-term potentiation (LTP) in the hippocampal CA1 field of anesthetized rats. Milnacipran-induced suppression was reversed by pretreatment with the selective 5-HT1A receptor antagonist WAY 100635 (0.1 mg/kg, i.v.) or the alpha1-adrenoceptor antagonist prazosin (1 and 10 microg/rat, i.c.v.). The alpha2-adrenoceptor antagonist idazoxan (5 mg/kg, i.p.) did not influence the milnacipran-induced synaptic responses. These data suggest that the inhibitory effects of milnacipran on LTP induction are mediated via both 5-HT1A receptors and alpha1-adrenoceptors. In other words, functional interaction between the serotonergic and noradrenergic neuronal systems is involved in alteration of the hippocampal synaptic plasticity, which may be implicated in the SNRI-induced therapeutic effect on psychiatric disorders.

  5. Long-term agroecosystem research in the Central Mississippi River Basin: dissolved nitrogen and phosphorus transport in a high-runoff-potential watershed

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Long-term nutrient monitoring data from agricultural watersheds are needed to determine if efforts to reduce nutrient transport from crop and pasture land have been effective. The objectives of this study were to: 1) summarize dissolved ammonium-N (NH4-N), nitrate-N (NO3-N), and orthophosphate-P (PO...

  6. Understanding the potential impact of climate change on long term soil carbon dynamics in tropical cropping systems - evidence from West Africa

    NASA Astrophysics Data System (ADS)

    Cretenet, Michel; Tittonell, Pablo; Guibert, Herve

    2010-05-01

    Long term experiments offer a unique opportunity to assess sustainability and temporal dynamics of biogeochemical cycles in agriculture, as well as the gradual impact on these of relatively slow processes such as climate change. Two long term experiments on annual cropping systems representing locally common crop rotations and cultural practices were established on two contrasting agroecological zones in Ivory Coast (in 1971) and in Mali (in 1965). These experiments were designed to assess the long-term productivity of these systems under different organic matter and nutrient management regimes, applying organic and mineral soil amendments alone or in combination. Organic soil amendments - such as animal manure, compost or plant material collected from the surroundings - were included in the experiments with the double purpose of adding nutrients for immediate crop production and adding organic matter inputs to the soil to restore (or maintain) its organic C content. Here, we provide an overview of the major trends in crop productivity and soil organic C observed in these experiments that illustrates the potential impact of climate change on the effectiveness of different measures to sustain agricultural productivity. Materials and methods Both experiments compared crop productivity on control plots without any soil amendment versus plots receiving organic matter, mineral fertilisers or both combined. The experiment at Gagnoa (southern Ivory Coast) was conducted during 23 years in a zone characterised by a bimodal rainfall regime (c. 1300 mm year-1) that allows two cropping seasons per year (Alfisols 15% clay). Every year maize was planted during the first rainy season. Organic matter was added as compost at a rate of 10 t ha-1 year-1, with or without application of 160 kg N ha-1 year-1 in mineral fertiliser (Chabalier, 1986). The experiment at N'Tarla (southern Mali) was conducted during 24 years in a zone of mono-modal rainfall (c. 900 mm year-1); Alfisols 5

  7. Effects of long-term in vitro culturing of transgenic bovine donor fibroblasts on cell viability and in vitro developmental potential after nuclear transfer.

    PubMed

    Bressan, F F; Miranda, M S; Bajgelman, M C; Perecin, F; Mesquita, L G; Fantinato-Neto, P; Merighe, G F K; Strauss, B E; Meirelles, F V

    2013-04-01

    SCNT experiments, no difference was observed between groups reconstructed with early or late-passage cells when fusion (63.1% and 49%), cleavage (67.7% and 69.9%), eight-cell embryo (36.4% and 44.4%) and blastocyst (21.6% and 20.8%) rates were compared. In conclusion, culture behavior was different between control and eGFP cells. However, when different in vitro culturing periods were compared, long-term cultured transgenic fetal fibroblasts remained competent for blastocyst production when used as nuclei donors in the nuclear transfer technique, a feature needed for the genetic manipulation of cell culture experiments aiming for transgenic animal production.

  8. Brazilian network for the surveillance of maternal potentially life threatening morbidity and maternal near-miss and a multidimensional evaluation of their long term consequences

    PubMed Central

    Cecatti, Jose G; Souza, João P; Parpinelli, Mary A; Haddad, Samira M; Camargo, Rodrigo S; Pacagnella, Rodolfo C; Silveira, Carla; Zanardi, Dulce T; Costa, Maria L; Pinto e Silva, João L; Passini, Renato; Surita, Fernanda G; Sousa, Maria H; Calderon, Iracema MP; Say, Lale; Pattinson, Robert C

    2009-01-01

    Background It has been suggested that the study of women who survive life-threatening complications related to pregnancy (maternal near-miss cases) may represent a practical alternative to surveillance of maternal morbidity/mortality since the number of cases is higher and the woman herself is able to provide information on the difficulties she faced and the long-term repercussions of the event. These repercussions, which may include sexual dysfunction, postpartum depression and posttraumatic stress disorder, may persist for prolonged periods of time, affecting women's quality of life and resulting in adverse effects to them and their babies. Objective The aims of the present study are to create a nationwide network of scientific cooperation to carry out surveillance and estimate the frequency of maternal near-miss cases, to perform a multicenter investigation into the quality of care for women with severe complications of pregnancy, and to carry out a multidimensional evaluation of these women up to six months. Methods/Design This project has two components: a multicenter, cross-sectional study to be implemented in 27 referral obstetric units in different geographical regions of Brazil, and a concurrent cohort study of multidimensional analysis. Over 12 months, investigators will perform prospective surveillance to identify all maternal complications. The population of the cross-sectional component will consist of all women surviving potentially life-threatening conditions (severe maternal complications) or life-threatening conditions (the maternal near miss criteria) and maternal deaths according to the new WHO definition and criteria. Data analysis will be performed in case subgroups according to the moment of occurrence and determining cause. Frequencies of near-miss and other severe maternal morbidity and the association between organ dysfunction and maternal death will be estimated. A proportion of cases identified in the cross-sectional study will comprise

  9. A 3-D Generalization of the Budyko Framework Captures the Mutual Interdependence Between Long-Term Mean Annual Precipitation, Actual and Potential Evapotranspiration

    NASA Astrophysics Data System (ADS)

    Carmona, A. M.; Poveda, G.

    2012-12-01

    We study the behavior of the 3-D parameter space defined by Φ =PET/P (so-called Aridity Index), Ψ =AET/P, and Ω =AET/PET, where P denotes mean annual precipitation, and PET and AET denote mean annual potential and actual evapotranspiration, respectively. Using information from the CLIMWAT 2.0 database (www.fao.org/nr/water/infores_databases_climwat.html) for P and PET, we estimate AET using both Budyko's and Turc's equations. Our results indicate that the well-known Budyko function that relates Φ vs.Ψ corresponds to a particular bi-dimensional cross-section of a broader coupling existing between Φ, Ψ and Ω (Figure 1a), and in turn of the mutual interdependence between P, PET and AET. The behavior of the three bi-dimensional projections are clearly parameterized by the remaining ortogonal parameter, such that: (i) the relation Φ vs. Ψ is defined by physically consistent varying values of Ω (Figure 1b); (ii) the relation Ω vs. Ψ is defined by physically consistent varying values of the Aridity Index,Φ (Figure 1c), and (iii) the relation Ω vs. Φ is defined by physically consistent varying values of Ψ (Figure 1d). Interestingly, we show that Φ and Ω are related by a power law, Φ~Ω-θ, with scaling exponent θ=1.15 (R2=0.91, n=3420) for the whole world (Figure 1d). Mathematical functions that model the three bi-dimensional projections and the surface defining the interdependence between Φ, Ψ and Ω will be presented. Our results provide a new framework to understand the coupling between the long-term mean annual water and energy balances in river basins, and the hydrological effects brought about by climate change, while taking into account the mutual interdependence between the three non-dimensional parameters Φ, Ψ and Ω, and in turn between P, PET and AET. Figure 1. (a) Three-dimensional rendering of sample values of Φ =PET/P (so-called Aridity Index), Ψ =AET/P, and Ω=AET/PET. Bi-dimensional projections of: (b) relation Φ vs.

  10. Potentiated gene regulation by methylphenidate plus fluoxetine treatment: Long-term gene blunting (Zif268, Homer1a) and behavioral correlates.

    PubMed

    Beverley, Joel A; Piekarski, Cassandra; Van Waes, Vincent; Steiner, Heinz

    2014-12-01

    Use of psychostimulants such as methylphenidate (Ritalin) in medical treatments and as cognitive enhancers in the healthy is increasing. Methylphenidate produces some addiction-related gene regulation in animal models. Recent findings show that combining selective serotonin reuptake inhibitor (SSRI) antidepressants such as fluoxetine with methylphenidate potentiates methylphenidate-induced gene regulation. We investigated the endurance of such abnormal gene regulation by assessing an established marker for altered gene regulation after drug treatments - blunting (repression) of immediate-early gene (IEG) inducibility - 14 days after repeated methylphenidate+fluoxetine treatment in adolescent rats. Thus, we measured the effects of a 6-day repeated treatment with methylphenidate (5 mg/kg), fluoxetine (5 mg/kg) or their combination on the inducibility (by cocaine) of neuroplasticity-related IEGs (Zif268, Homer1a) in the striatum, by in situ hybridization histochemistry. Repeated methylphenidate treatment alone produced modest gene blunting, while fluoxetine alone had no effect. In contrast, fluoxetine given in conjunction with methylphenidate produced pronounced potentiation of methylphenidate-induced blunting for both genes. This potentiation was seen in many functional domains of the striatum, but was most robust in the lateral, sensorimotor striatum. These enduring molecular changes were associated with potentiated induction of behavioral stereotypies in an open-field test. For illicit psychostimulants, blunting of gene expression is considered part of the molecular basis of addiction. Our results thus suggest that SSRIs such as fluoxetine may increase the addiction liability of methylphenidate. Key words: cognitive enhancer, dopamine, serotonin, gene expression, psychostimulant, SSRI antidepressant, striatum.

  11. The E3 Ligase APC/C-Cdh1 Is Required for Associative Fear Memory and Long-Term Potentiation in the Amygdala of Adult Mice

    ERIC Educational Resources Information Center

    Pick, Joseph E.; Malumbres, Marcos; Klann, Eric

    2013-01-01

    The anaphase promoting complex/cyclosome (APC/C) is an E3 ligase regulated by Cdh1. Beyond its role in controlling cell cycle progression, APC/C-Cdh1 has been detected in neurons and plays a role in long-lasting synaptic plasticity and long-term memory. Herein, we further examined the role of Cdh1 in synaptic plasticity and memory by generating…

  12. Long term complications of diabetes

    MedlinePlus

    ... medlineplus.gov/ency/patientinstructions/000327.htm Long-term complications of diabetes To use the sharing features on this page, ... other tests. All these may help you keep complications of diabetes away. You will need to check your blood ...

  13. Long Term Surface Salinity Measurements

    NASA Technical Reports Server (NTRS)

    Schmitt, Raymond W.; Brown, Neil L.

    2005-01-01

    Our long-term goal is to establish a reliable system for monitoring surface salinity around the global ocean. Salinity is a strong indicator of the freshwater cycle and has a great influence on upper ocean stratification. Global salinity measurements have potential to improve climate forecasts if an observation system can be developed. This project is developing a new internal field conductivity cell that can be protected from biological fouling for two years. Combined with a temperature sensor, this foul-proof cell can be deployed widely on surface drifters. A reliable in-situ network of surface salinity sensors will be an important adjunct to the salinity sensing satellite AQUARIUS to be deployed by NASA in 2009. A new internal-field conductivity cell has been developed by N Brown, along with new electronics. This sensor system has been combined with a temperature sensor to make a conductivity - temperature (UT) sensor suitable for deployment on drifters. The basic sensor concepts have been proven on a high resolution CTD. A simpler (lower cost) circuit has been built for this application. A protection mechanism for the conductivity cell that includes antifouling protection has also been designed and built. Mr. A.Walsh of our commercial partner E-Paint has designed and delivered time-release formulations of antifoulants for our application. Mr. G. Williams of partner Clearwater Instrumentation advised on power and communication issues and supplied surface drifters for testing.

  14. [Fetal pain: immediate and long term consequences].

    PubMed

    Houfflin Debarge, Véronique; Dutriez, Isabelle; Pusniak, Benoit; Delarue, Eléonore; Storme, Laurent

    2010-06-01

    Several situations are potentially painful for fetuses, such as malformations and invasive procedures. Nociceptive pathways are known to be functional at 26 weeks. Even if it is not possible to evaluate the fetal experience of pain, it is essential to examine its immediate and long-term consequences. As early as the beginning of the second trimester, hemodynamic and hormonal responses are observed following fetal nociceptive stimulation, In experimental studies, long-term changes have been noted in the corticotrop axis, subsequent responses to pain, and behavior after perinatal nociceptive stimulation.

  15. Potential for Local Fertilization: A Benthocosm Test of Long-Term and Short-Term Effects of Mussel Excretion on the Plankton

    PubMed Central

    Granados, Monica; Duffy, Sean; Robert, Pauline; Péquin, Bérangère; Mohit, Vani; McKindsey, Christopher W.; Archambault, Philippe; Myrand, Bruno; Lovejoy, Connie; Tremblay, Réjean; Plourde, Stéphane; Fussmann, Gregor F.

    2016-01-01

    Mussel aquaculture has expanded worldwide and it is important to assess its impact on the water column and the planktonic food web to determine the sustainability of farming practices. Mussel farming may affect the planktonic food web indirectly by excreting bioavailable nutrients in the water column (a short-term effect) or by increasing nutrient effluxes from biodeposit-enriched sediments (a long-term effect). We tested both of these indirect effects in a lagoon by using plankton-enclosing benthocosms that were placed on the bottom of a shallow lagoon either inside of a mussel farm or at reference sites with no history of aquaculture. At each site, half of the benthocosms were enriched with seawater that had held mussels (excretion treatment), the other half received non-enriched seawater as a control treatment. We monitored nutrients ([PO43-] and [NH4+]), dissolved oxygen and plankton components (bacteria, the phytoplankton and the zooplankton) over 5 days. We found a significant relationship between long-term accumulation of mussel biodeposits in sediments, water-column nutrient concentrations and plankton growth. Effects of mussel excretion were not detected, too weak to be significant given the spatial and temporal variability observed in the lagoon. Effects of mussels on the water column are thus likely to be coupled to benthic processes in such semi-enclosed water bodies. PMID:27249793

  16. Epinephrine: a short- and long-term regulator of stress and development of illness : a potential new role for epinephrine in stress.

    PubMed

    Wong, Dona Lee; Tai, T C; Wong-Faull, David C; Claycomb, Robert; Meloni, Edward G; Myers, Karyn M; Carlezon, William A; Kvetnansky, Richard

    2012-07-01

    Epinephrine (Epi), which initiates short-term responses to cope with stress, is, in part, stress-regulated via genetic control of its biosynthetic enzyme, phenylethanolamine N-methyltransferase (PNMT). In rats, immobilization (IMMO) stress activates the PNMT gene in the adrenal medulla via Egr-1 and Sp1 induction. Yet, elevated Epi induced by acute and chronic stress is associated with stress induced, chronic illnesses of cardiovascular, immune, cancerous, and behavioral etiologies. Major sources of Epi include the adrenal medulla and brainstem. Although catecholamines do not cross the blood-brain barrier, circulating Epi from the adrenal medulla may communicate with the central nervous system and stress circuitry by activating vagal nerve β-adrenergic receptors to release norepinephrine, which could then stimulate release of the same from the nucleus tractus solitarius and locus coeruleus. In turn, the basal lateral amygdala (BLA) may activate to stimulate afferents to the hypothalamus, neocortex, hippocampus, caudate nucleus, and other brain regions sequentially. Recently, we have shown that repeated IMMO or force swim stress may evoke stress resiliency, as suggested by changes in expression and extinction of fear memory in the fear-potentiated startle paradigm. However, concomitant adrenergic changes seem stressor dependent. Present studies aim to identify stressful conditions that elicit stress resiliency versus stress sensitivity, with the goal of developing a model to investigate the potential role of Epi in stress-associated illness. If chronic Epi over expression does elicit illness, possibilities for alternative therapeutics exist through regulating stress-induced Epi expression, adrenergic receptor function and/or corticosteroid effects on Epi, adrenergic receptors and the stress axis.

  17. Long-term parenteral nutrition

    PubMed Central

    Ladefoged, Karin; Jarnum, Stig

    1978-01-01

    Nineteen patients (11 women and eight men) aged 20-68 received long-term parenteral nutrition, mostly at home, for six to 63 months (mean 19 months). Indications for LTPN were extensive, active Crohn's disease in three patients, intestinocutaneous fistulas in three, and short-bowel syndrome in the remaining 13 patients. Subclavian or intra-atrial (Broviac) catheters were most commonly used, for which the average life was four and seven months respectively. Complications of long-term parenteral nutrition included pneumothorax in four out of 48 subclavian vein punctures. Catheter-induced thrombosis of central veins was shown by phlebography 17 times in nine patients, and eight episodes of total occlusion occurred. Two of these patients had pulmonary infarction. Nineteen episodes of catheter sepsis occurred in 11 patients, but only one was fatal. Complications related to intestinal disease included intra-abdominal abscesses and intestinal fistulas, and disturbances of liver function. Five patients died, though in only two was death related to long-term parenteral nutrition. One of these patients died from catheter sepsis, the other had subdural haematoma possibly caused by anticoagulant treatment. Eight of the 14 surviving patients still needed parenteral nutrition. All received a disability pension, but six had an acceptable quality of life with almost normal social activities. Despite problems such as difficulties in maintaining standardised infusion programmes, it was concluded that long-term parenteral nutrition at home is practicable and consistent with an acceptable quality of life. ImagesFIG 2 PMID:98199

  18. Potential long-term effects of a mind-body intervention for women with major depressive disorder: sustained mental health improvements with a pilot yoga intervention.

    PubMed

    Kinser, Patricia Anne; Elswick, R K; Kornstein, Susan

    2014-12-01

    Despite pharmacologic and psychotherapeutic advances over the past decades, many individuals with major depressive disorder (MDD) experience recurrent depressive episodes and persistent depressive symptoms despite treatment with the usual care. Yoga is a mind-body therapeutic modality that has received attention in both the lay and research literature as a possible adjunctive therapy for depression. Although promising, recent findings about the positive mental health effects of yoga are limited because few studies have used standardized outcome measures and none of them have involved long-term follow-up beyond a few months after the intervention period. The goal of our research study was to evaluate the feasibility, acceptability, and effects of a yoga intervention for women with MDD using standardized outcome measures and a long follow-up period (1year after the intervention). The key finding is that previous yoga practice has long-term positive effects, as revealed in both qualitative reports of participants' experiences and in the quantitative data about depression and rumination scores over time. Although generalizability of the study findings is limited because of a very small sample size at the 1-year follow-up assessment, the trends in the data suggest that exposure to yoga may convey a sustained positive effect on depression, ruminations, stress, anxiety, and health-related quality of life. Whether an individual continues with yoga practice, simple exposure to a yoga intervention appears to provide sustained benefits to the individual. This is important because it is rare that any intervention, pharmacologic or non-pharmacologic, for depression conveys such sustained effects for individuals with MDD, particularly after the treatment is discontinued.

  19. Long-term opioid therapy reconsidered.

    PubMed

    Von Korff, Michael; Kolodny, Andrew; Deyo, Richard A; Chou, Roger

    2011-09-06

    In the past 20 years, primary care physicians have greatly increased prescribing of long-term opioid therapy. However, the rise in opioid prescribing has outpaced the evidence regarding this practice. Increased opioid availability has been accompanied by an epidemic of opioid abuse and overdose. The rate of opioid addiction among patients receiving long-term opioid therapy remains unclear, but research suggests that opioid misuse is not rare. Recent studies report increased risks for serious adverse events, including fractures, cardiovascular events, and bowel obstruction, although further research on medical risks is needed. New data indicate that opioid-related risks may increase with dose. From a societal perspective, higher-dose regimens account for the majority of opioids dispensed, so cautious dosing may reduce both diversion potential and patient risks for adverse effects. Limiting long-term opioid therapy to patients for whom it provides decisive benefits could also reduce risks. Given the warning signs and knowledge gaps, greater caution and selectivity are needed in prescribing long-term opioid therapy. Until stronger evidence becomes available, clinicians should err on the side of caution when considering this treatment.

  20. Long-term data archiving

    SciTech Connect

    Moore, David Steven

    2009-01-01

    Long term data archiving has much value for chemists, not only to retain access to research and product development records, but also to enable new developments and new discoveries. There are some recent regulatory requirements (e.g., FDA 21 CFR Part 11), but good science and good business both benefit regardless. A particular example of the benefits of and need for long term data archiving is the management of data from spectroscopic laboratory instruments. The sheer amount of spectroscopic data is increasing at a scary rate, and the pressures to archive come from the expense to create the data (or recreate it if it is lost) as well as its high information content. The goal of long-term data archiving is to save and organize instrument data files as well as any needed meta data (such as sample ID, LIMS information, operator, date, time, instrument conditions, sample type, excitation details, environmental parameters, etc.). This editorial explores the issues involved in long-term data archiving using the example of Raman spectral databases. There are at present several such databases, including common data format libraries and proprietary libraries. However, such databases and libraries should ultimately satisfy stringent criteria for long term data archiving, including readability for long times into the future, robustness to changes in computer hardware and operating systems, and use of public domain data formats. The latter criterion implies the data format should be platform independent and the tools to create the data format should be easily and publicly obtainable or developable. Several examples of attempts at spectral libraries exist, such as the ASTM ANDI format, and the JCAMP-DX format. On the other hand, proprietary library spectra can be exchanged and manipulated using proprietary tools. As the above examples have deficiencies according to the three long term data archiving criteria, Extensible Markup Language (XML; a product of the World Wide Web

  1. Growth and metal removal potential of a Phormidium bigranulatum-dominated mat following long-term exposure to elevated levels of copper.

    PubMed

    Kumar, Dhananjay; Gaur, J P

    2014-09-01

    The present study explores the tolerance and metal removal response of a well-developed 2-week-old Phormidium mat after long-term exposure to Cu(2+)-enriched medium. Cu(2+) enrichment inhibited increase in mat biomass in a concentration-dependent manner. Mat area and the number of entrapped air bubbles decreased as Cu(2+) concentration increased in the medium. Decrease in number of air bubbles obviously reflects the adverse effect of Cu(2+) on photosynthetic performance of the mat. Metal enrichment did not substantially alter the amount of pigments, such as chlorophyll a, chlorophyll b, carotenoids, and phycocyanin, in the mat. Enhancement of Cu(2+) concentration in the medium led to changes in species composition of the test mat; however, Phormidium bigranulatum always remained the dominant organism. Relative share of green algae and some cyanobacterial taxa, namely, Lyngbya sp. and Oscillatoria tenuis, in the mat were increased by Cu(2+) enrichment. The mat successfully removed 80 to 94 % Cu(2+) from the growth medium containing 10 to 100 μM Cu(2+). Extracellular polysaccharides, whose share increased in the mat community after metal addition, seem to have contributed substantially to metal binding by the mat biomass.

  2. The potential use of cholestyramine to reduce the risk of developing Clostridium difficile-associated diarrhoea in patients receiving long-term intravenous ceftriaxone.

    PubMed

    Puri, B K; Hakkarainen-Smith, J S; Monro, Jean A

    2015-01-01

    Intravenous pharmacotherapy with the third-generation cephalosporin ceftriaxone is unfortunately associated with a relatively high incidence of Clostridium difficile-associated diarrhoea. Ch