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LTP Induction (ltp + induction)
Selected AbstractsCOX-2, but not COX-1, activity is necessary for the induction of perforant path long-term potentiation and spatial learning in vivoEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2008T. R. Cowley Abstract The objectives of this research were to investigate the role played by the enzyme cyclooxygenase (COX) in learning and memory, synaptic plasticity and synaptic transmission in the rat brain in vivo. Male Wistar rats were treated with isoform-selective inhibitors for COX-1 and COX-2, either chronically and tested in the watermaze or acutely before electrophysiological recordings were made. We found a significant impairment in acquisition of the watermaze with inhibition of COX-2. Furthermore, we found COX-2 but not COX-1 inhibition significantly blocked long-term potentiation (LTP) induction but had no effect on already established LTP. Moreover, exogenous replacement of the main metabolite of COX-2 activity, PGE2, was sufficient to restore LTP induction and for normal downstream signalling to ensue, namely extracellular signalling-regulated kinase (ERK)-phosphorylation and c-FOS expression. We conclude that endogenous basal levels of PGE2 resulting from COX-2 but not COX-1 activity are necessary for synaptic plasticity and memory acquisition. [source] Nicotine withdrawal suppresses nicotinic modulation of long-term potentiation induction in the hippocampal CA1 regionEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 10 2006Yoshihiko Yamazaki Abstract We have previously reported that acute and chronic nicotine exposure lower the threshold for long-term potentiation (LTP) induction in the rat hippocampal CA1 region, and acute application of nicotine in the chronic-nicotine-treated hippocampus further reduces the threshold. However, it is unknown how withdrawal from chronic nicotine exposure affects the induction of LTP. Here, we show that, following nicotine withdrawal, the threshold for LTP induction fluctuates before returning to the basal level and acute nicotine is no longer effective in lowering the threshold at 4 days after withdrawal. Chronic nicotine-induced enhancement of N -methyl- d -aspartate receptor responses slowly diminishes and returns to the control level by 8 days of withdrawal. In 4-day-withdrawn hippocampi, there is functional up-regulation of postsynaptic ,7 nicotinic acetylcholine receptors (nAChRs) on interneurons in the stratum radiatum, whereas the release of ,-aminobutyric acid from their terminals is reduced. In both control and chronic nicotine-exposed hippocampi, acute nicotine depresses monosynaptic inhibitory postsynaptic currents recorded in pyramidal cells but has almost no effect at 4 days of withdrawal. The lack of effect is due, at least in part, to the loss of a presynaptic nicotine effect. These withdrawal-induced changes are accompanied by decreases in normal nicotine-induced enhancement of N -methyl- d -aspartate receptor responses, which may be responsible for the lack of acute nicotine-mediated facilitation of LTP induction in 4-day-withdrawn hippocampi. These withdrawal-induced changes may contribute to the cellular basis of unpleasant withdrawal symptoms and, thus, nicotine dependence. [source] A point mutant of GAP-43 induces enhanced short-term and long-term hippocampal plasticityEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2002S. Hulo Abstract The growth-associated protein GAP-43 (or neuromodulin or B-50) plays a critical role during development in mechanisms of axonal growth and formation of synaptic networks. At later times, GAP-43 has also been implicated in the regulation of synaptic transmission and properties of plasticity such as long-term potentiation. In a molecular approach, we have analyzed transgenic mice overexpressing different mutated forms of GAP-43 or deficient in GAP-43 to investigate the role of the molecule in short-term and long-term plasticity. We report that overexpression of a mutated form of GAP-43 that mimics constitutively phosphorylated GAP-43 results in an enhancement of long-term potentiation in CA1 hippocampal slices. This effect is specific, because LTP was affected neither in transgenic mice overexpressing mutated forms of non-phosphorylatable GAP-43 nor in GAP-43 deficient mice. The increased LTP observed in transgenic mice expressing a constitutively phosphorylated GAP-43 was associated with an increased paired-pulse facilitation as well as an increased summation of responses during high frequency bursts. These results indicate that, while GAP-43 is not necessary for LTP induction, its phosphorylation may regulate presynaptic properties, thereby affecting synaptic plasticity and the induction of LTP. [source] Properties of LTD and LTP of retinocollicular synaptic transmission in the developing rat superior colliculusEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 9 2002Fu-Sun Lo Abstract The developing retinocollicular pathway undergoes synaptic refinement in order to form the precise retinotopic pattern seen in adults. To study the mechanisms which underlie refinement, we investigated long-term changes in retinocollicular transmission in rats aged P0,P25. Field potentials (FPs) in the superior colliculus (SC) were evoked by stimulation of optic tract fibers in an in vitro isolated brainstem preparation. High intensity stimulation induced long-term depression (LTD) in the SC after both low (1000 stimuli at 1 Hz) and higher (1000 stimuli at 50 Hz) frequency stimulation. The induction of LTD was independent of activation of NMDA and GABAA receptors, because d -APV (100 µM) and bicuculline (10 µM) did not block LTD. Induction of LTD was dependent upon activation of l -type Ca2+ channels as 10 µM nitrendipine, an l -type Ca2+ channel blocker, significantly decreased the magnitude of LTD. LTD was down-regulated during development. LTD magnitude was greatest in rats aged P0,P9 and significantly less in rats aged P10,P25. Long-term potentiation (LTP) was induced by low intensity stimulation and only after high frequency tetanus (1000 stimuli at 50 Hz). LTP was NMDA receptor dependent because d -APV (100 ,M) completely abolished it. LTP induction was also blocked by the l -type Ca2+ channel blocker nitrendipine. The magnitude of LTP first increased with age, being significantly greater at P7,P13 than at P0,3 and then decreased at P23,25. In summary, both LTD and LTP are present during retinocollicular pathway refinement, but have different transmitter and ionic mechanisms and time courses of expression. [source] Competitive interactions between endogenous LTD and LTP in the hippocampus underlie the storage of emotional memories and stress-induced amnesiaHIPPOCAMPUS, Issue 8 2005David M. Diamond Abstract This speculative review serves two purposes. First, it as an extension of the ideas we developed in a previous review (Diamond et al., Hippocampus, 2004;14:281,291), and second, it is a rebuttal to Abraham's (Hippocampus, 2004;14:675,676) critique of that review. We had speculated on the functional significance of the finding that post-training LTP induction produces retrograde amnesia. We noted the similarities between the findings that strong tetanizing stimulation can produce LTP and retrograde amnesia, and that a strong emotional experience can produce a long-lasting memory and retrograde amnesia, as well. The commonalities between LTP induction and emotional learning provided the basis of our hypothesis that an emotional experience generates endogenous LTD/depotentiation, which reverses synaptic plasticity formed during previous learning experiences, and endogenous LTP, which underlies the storage of new information. Abraham raised several concerns with our review, including the criticism that our speculation "falters because there is no evidence that stress causes LTD or depotentiation," and that research on stress and hippocampus has "failed to report any LTP-like changes." Abraham's points are well-taken because stress, in isolation, does not appear to generate long-lasting changes in baseline measures of hippocampal excitability. Here, within the context of a reply to Abraham's critique, we have provided a review of the literature on the influence of stress, novelty, fear conditioning, and the retrieval of emotional memories on cognitive and physiological measures of hippocampal functioning. An emphasis of this review is our hypothesis that endogenous forms of depotentiation, LTD and LTP are generated only when arousing experiences occur in conjunction with memory-related activation of the hippocampus and amygdala. We conclude with speculation that interactions among the different forms of endogenous plasticity underlie a form of competition by synapses and memories for access to retrieval resources. © 2005 Wiley-Liss, Inc. [source] Muscarinic signaling is required for spike-pairing induction of long-term potentiation at rat Schaffer collateral-CA1 synapsesHIPPOCAMPUS, Issue 4 2004Scott V. Adams Abstract Cholinergic input from the basal forebrain and septum to the hippocampus is well known to be critical in learning and memory. Muscarinic induction of theta-frequency oscillations may synchronize pre- and postsynaptic firing and thereby enhance plasticity in the hippocampus. Previous studies have demonstrated that muscarinic activation facilitates long-term potentiation (LTP) induced with tetanus in vitro. In the present study, we tested the role of muscarinic receptor activity in the induction of LTP beyond effects on spike timing by using a spike-pairing (SP) method at Schaffer collateral-CA1 synapses in rat hippocampal slices. Pairings of pre- and postsynaptic action potentials (APs) have been shown to induce LTP when the presynaptic AP precedes the postsynaptic AP by 5,15 ms, but contribution of muscarinic co-activation has not been ruled out. We demonstrate that the mAChR antagonist atropine abolishes LTP induction by SP. Surprisingly, prolonged exposure to the mAChR agonist carbachol inhibits LTP induction by SP, perhaps because of receptor desensitization. These results demonstrate an essential role of cholinergic signaling in this form of hippocampal plasticity. © 2004 Wiley-Liss, Inc. [source] Role of phosphorylation of ERK in induction and maintenance of LTP of the C-fiber evoked field potentials in spinal dorsal hornJOURNAL OF NEUROSCIENCE RESEARCH, Issue 5 2006Wen-Jun Xin Abstract Previous works have shown that activation of extracellular signal-regulated kinase (ERK)/cAMP response element binding protein (CREB) pathway is essential for long-term potentiation (LTP) in hippocampus. In the present study, the role of the ERK/CREB pathway in LTP of C-fiber evoked field potentials in spinal dorsal horn, which is relevant to pathologic pain, was investigated in adult rats. Western blotting analysis showed that the protein level of phosphorylated ERK (p-ERK) in ipsilateral spinal dorsal horn was transiently increased after LTP induction, starting at 15 min and returning to control at 60 min after tetanic stimulation and that the protein level of p-CREB increased at 30 min, persisting for at least 3 hr after LTP induction. Double immunofluorescence staining showed that p-ERK and p-CREB were only located in neurons but not in glial cells in the spinal dorsal horn after LTP induction. More importantly, we found that spinal application of PD 98059 (100 ,M), a selective MEK inhibitor, at 30 min before tetanic stimulation blocked LTP induction and prevented the increase in p-ERK and p-CREB in spinal dorsal horn. When applied 15 min after LTP induction, PD98059 reversed established LTP. The drug, however, did not affect the spinal LTP, when applied at 30 min after LTP. Our results suggested that activation of ERK/CREB pathway in spinal dorsal neurons is necessary for induction and maintenance of long-term potentiation of the C-fiber evoked field potentials. © 2006 Wiley-Liss, Inc. [source] Ethanol Acutely Inhibits Ionotropic Glutamate Receptor-Mediated Responses and Long-Term Potentiation in the Developing CA1 HippocampusALCOHOLISM, Issue 4 2010Michael P. Puglia 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- to 9-day-old rats. Extracellular and patch-clamp electrophysiological recording techniques were used to characterize the acute effects of EtOH on ,-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:, Ethanol (40 and 80 mM) inhibited AMPAR- and NMDAR-mediated field excitatory postsynaptic potentials (fEPSPs). EtOH (80 mM) also reduced AMPAR-mediated fEPSPs in the presence of an inhibitor of Ca2+ permeable AMPARs. The effect of 80 mM EtOH on NMDAR-mediated fEPSPs was significantly greater in the 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. [source] Ethanol Attenuates the HFS-Induced, ERK-Mediated LTP in a Dose-Dependent Manner in Rat StriatumALCOHOLISM, Issue 1 2009Gui Qin Xie Background:, The striatum has been implicated to play a role in the control of voluntary behavior, and striatal synaptic plasticity is involved in instrumental learning. Ethanol is known to alter synaptic plasticity, in turn altering the behavior of human and animals. However, it remains unclear whether the striatum plays a role in the effects of ethanol on the central nervous system. The objective of this investigation was to study the effects of acute perfusion of ethanol on long-term potentiation (LTP) to elucidate the mechanisms of addictive drugs in the striatum. In addition, we investigated the contribution of intracellular extracellular signal regulated protein kinase (ERK) signaling pathway to corticostriatal LTP induction. Methods:, The stimulation evoked population spikes (PS) were recorded from the dorsomedial striatum (DMS) slices of rat using the extracellular recording technique. The LTP in DMS slices was induced by high-frequency stimulation (HFS). The ERK level of the DMS was assessed with the Western blot technique. Results:, U0126, the inhibitor of ERK, eliminated or significantly attenuated the LTP induced by HFS of the PS in the DMS. MK801 and APV, N -methyl- d -aspartic acid receptor (NMDAR) antagonists, inhibited the induction of striatal LTP, and HFS-induced ERK activation decreased in the slices treated with MK801 in the DMS. Clinically relevant concentrations of ethanol (22 to 88 mM) dose-dependently attenuated the HFS-induced striatal LTP and ERK activation in this brain region. Conclusions:, The LTP of the PS in the DMS is, at least partly, mediated by the ERK pathway coupling to NMDARs. Ethanol attenuated the HFS-induced, ERK-mediated LTP in a dose-dependent manner in this brain region. These results indicate that ethanol may change the synaptic plasticity of corticostriatal circuits underlying the learning of goal-directed instrumental actions, which is mediated by an intracellular ERK signaling pathway associated with NMDARs. [source] Functional contributions of synaptically localized NR2B subunits of the NMDA receptor to synaptic transmission and long-term potentiation in the adult mouse CNSTHE JOURNAL OF PHYSIOLOGY, Issue 10 2008Hideki Miwa The NMDA-type glutamate receptor is a heteromeric complex composed of the NR1 and at least one of the NR2 subunits. Switching from the NR2B to the NR2A subunit is thought to underlie functional alteration of the NMDA receptor during synaptic maturation, and it is generally believed that it results in preferential localization of NR2A subunits on the synaptic site and that of NR2B subunits on the extracellular site in the mature brain. It has also been proposed that activation of the NR2A and NR2B subunits results in long-term potentiation (LTP) and long-term depression (LTD), respectively. Furthermore, recent reports suggest that synaptic and extrasynaptic receptors may have distinct roles in synaptic plasticity as well as in gene expression associated with neuronal death. Here, we have investigated whether NR2B subunit-containing receptors are present and functional at mature synapses in the lateral nucleus of the amygdala (LA) and the CA1 region of the hippocampus, comparing their properties between the two brain regions. We have found, in contrast to the above hypotheses, that the NR2B subunit significantly contributes to synaptic transmission as well as LTP induction. Furthermore, its contribution is greater in the LA than in the CA1 region, and biophysical properties of NMDA receptors and the NR2B/NR2A ratio are different between the two brain regions. These results indicate that NR2B subunit-containing NMDA receptors accumulate on the synaptic site and are responsible for the unique properties of synaptic function and plasticity in the amygdala. [source] | ||||||||||