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Xian-guo Liu - One of the best experts on this subject based on the ideXlab platform.
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Role of phosphorylation of ERK in Induction and maintenance of LTP of the C-fiber evoked field potentials in spinal dorsal horn.
Journal of neuroscience research, 2006Co-Authors: Wen Jun Xin, Hong Wei Yang, Tong Zhang, Qing-juan Gong, Ying Zang, Xian-guo LiuAbstract: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 microM), 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.
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Diazepam inhibits the Induction and maintenance of LTP of C-fiber evoked field potentials in spinal dorsal horn of rats
Neuropharmacology, 2005Co-Authors: Hongmei Zhang, Tong Zhang, Li Jun Zhou, Yifan Han, Xian-guo LiuAbstract:Abstract The benzodiazepine diazepam impairs memory and long-term potentiation (LTP) in the hippocampus. Here, we investigate the effect of diazepam on LTP of C-fiber evoked field potentials in spinal dorsal horn, which is relevant to pathological pain. LTP of C-fiber evoked field potentials was recorded in the superficial layers of spinal dorsal horn in urethane-anesthetized Sprague–Dawley rats. Diazepam was applied locally at the recording spinal segments before and after LTP Induction by tetanic stimulation. We found (1) Diazepam completely blocked LTP Induction. (2) Diazepam and midazolam reversed spinal LTP, when applied at 30 min after LTP Induction and depressed but could not reverse spinal LTP, when applied at 3 h after LTP Induction. (3) Pretreatment with benzodiazepine receptor antagonist flumazenil or GABAA receptor antagonist bicuculline completely blocked the inhibitory effects of diazepam on spinal LTP. In contrast, when the inhibitory effect of diazepam was fully established, neither of these antagonists was capable of reversing the inhibition by diazepam. (4) Spinal application of the GABAA receptor agonist 3-amino-1-propanesulfonic acid (3-APSA) at a dose of 50 μg, produced a transient inhibition of spinal LTP. These results suggest that diazepam might prevent and depress spinal plastic change produced by noxious stimulation via activation of the GABAA–benzodiazepine receptor complex.
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Roles of CaMKII, PKA, and PKC in the Induction and Maintenance of LTP of C-Fiber-Evoked Field Potentials in Rat Spinal Dorsal Horn
Journal of neurophysiology, 2003Co-Authors: Hong Wei Yang, Hongmei Zhang, Wen Jun Xin, Tong Zhang, Li Jun Zhou, Xian-guo LiuAbstract:Long-term potentiation (LTP) of C-fiber-evoked field potentials in spinal dorsal horn may be relevant to hyperalgesia, an increased response to noxious stimulation. The mechanism underlying this form of synaptic plasticity is, however, still unclear. Considerable evidence has shown that calcium/calmodulin-dependent protein kinase II (CaMKII), protein kinase A (PKA), and protein kinase C (PKC) are important for LTP in hippocampus. In this study, the roles of these three protein kinases in the Induction and maintenance of LTP of C-fiber-evoked field potentials were evaluated by application of specific inhibitors of CaMKII (KN-93 and AIP), PKA (Rp-CPT-cAMPS), and PKC (chelerythrine and Go 6983) at the recording segments before and after LTP Induction in urethane-anesthetized Sprague-Dawley rats. We found both KN-93 and AIP, when applied at 30 min prior to tetanic stimulation, completely blocked LTP Induction. At 30 min after LTP Induction, KN-93 and AIP reversed LTP completely, and at 60 min after LTP Induction, they depressed spinal LTP in most rats tested. Three hours after LTP Induction, however, KN-93 or AIP did not affect the spinal LTP. Rp-CPT-cAMPS, chelerythrine, and Go 6983 blocked the spinal LTP when applied at 30 min before tetanic stimulation and reversed LTP completely at 15 min after LTP Induction. In contrast, at 30 min after LTP Induction, the drugs never affected the spinal LTP. These results suggest that activation of CaMKII, PKA, and PKC may be crucial for the Induction and the early-phase but not for the late-phase maintenance of the spinal LTP.
Tai-zhen Han - One of the best experts on this subject based on the ideXlab platform.
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nr2a containing nmda receptors are required for l LTP Induction and depotentiation in ca1 region of hippocampal slices
European Journal of Neuroscience, 2009Co-Authors: Li Zhang, Kai Meng, Tai-zhen HanAbstract:Abstract Long-term potentiation (LTP) is a well-characterized form of synaptic plasticity that fulfills many of the criteria for the neural correlate of memory. LTP reversal (or depotentiation, DP) is thought to correlate with prevention or elimination of memory storage. LTP during and immediately after Induction can be easily reversed by afferent stimulation, when applied within the optimal time window. The aim of the present study was to determine whether later-phase LTP (L-LTP) could be reversed by special patterned stimulation applied at 2 h after LTP Induction, as well as to characterize the receptor mechanisms underlying this reversal. Field excitatory postsynaptic potentials evoked by Schaffer collateral stimulation were recorded from the CA1 subfield of adult rat hippocampal slices. Results demonstrated that stable LTP, which was induced by six theta-burst stimulations, was mediated by NR2A-containing N-methyl-d-aspartate receptors (NMDARs). This L-LTP was partially reversed by high-intensity paired-pulse low-frequency stimulation (HI-PP-LFS) and was inhibited by Zn(2+) (30 nm), a voltage-independent NR2A-NMDAR antagonist. However, NR2B-NMDAR antagonists (Ro 25-6981, 1 mum) displayed no effect on L-LTP reversal. L-LTP partial reversal was also induced by HI-PP-LFS, when the protein synthesis inhibitors anisomycin (25 microm) and cycloheximide (60 microm) were applied following LTP Induction. These results suggested that NR2A-containing NMDARs are required for L-LTP Induction and DP in the hippocampal CA1 area of adult rats. Moreover, HI-PP-LFS was an effective stimulation pattern to induce DP.
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NR2A‐containing NMDA receptors are required for L‐LTP Induction and depotentiation in CA1 region of hippocampal slices
The European journal of neuroscience, 2009Co-Authors: Li Zhang, Kai Meng, Tai-zhen HanAbstract:Abstract Long-term potentiation (LTP) is a well-characterized form of synaptic plasticity that fulfills many of the criteria for the neural correlate of memory. LTP reversal (or depotentiation, DP) is thought to correlate with prevention or elimination of memory storage. LTP during and immediately after Induction can be easily reversed by afferent stimulation, when applied within the optimal time window. The aim of the present study was to determine whether later-phase LTP (L-LTP) could be reversed by special patterned stimulation applied at 2 h after LTP Induction, as well as to characterize the receptor mechanisms underlying this reversal. Field excitatory postsynaptic potentials evoked by Schaffer collateral stimulation were recorded from the CA1 subfield of adult rat hippocampal slices. Results demonstrated that stable LTP, which was induced by six theta-burst stimulations, was mediated by NR2A-containing N-methyl-d-aspartate receptors (NMDARs). This L-LTP was partially reversed by high-intensity paired-pulse low-frequency stimulation (HI-PP-LFS) and was inhibited by Zn(2+) (30 nm), a voltage-independent NR2A-NMDAR antagonist. However, NR2B-NMDAR antagonists (Ro 25-6981, 1 mum) displayed no effect on L-LTP reversal. L-LTP partial reversal was also induced by HI-PP-LFS, when the protein synthesis inhibitors anisomycin (25 microm) and cycloheximide (60 microm) were applied following LTP Induction. These results suggested that NR2A-containing NMDARs are required for L-LTP Induction and DP in the hippocampal CA1 area of adult rats. Moreover, HI-PP-LFS was an effective stimulation pattern to induce DP.
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NR2A-containing NMDA receptors are required for LTP Induction in rat dorsolateral striatum in vitro.
Brain research, 2009Co-Authors: Tai-zhen HanAbstract:Abstract N-methyl- d -aspartate receptors (NMDARs) have been implicated in various forms of synaptic plasticity. In recent years, studies have been shown that NMDA receptor subunits play different roles in several forms of NMDAR-dependent synaptic plasticity. However, the contribution of NR2A and NR2B subunits in the Induction of long-term potentiation (LTP) in the corticostriatal pathway remains unclear. The present study used patch-clamp recordings to study the role of NR2A-containing and NR2B-containing NMDARs in LTP Induction in corticostriatal slices from 13–14-day old rats. High-frequency stimulation (HFS) of the corticostriatal pathway readily induced LTP of excitatory postsynaptic currents (EPSCs), and D-APV, a selective NMDAR antagonist, blocked LTP. Moreover, NR2B-containing NMDAR antagonists (Ro 25-6981 and ifenprodil) displayed no influence on LTP Induction. However, LTP was not inducible in the presence of Zn2+, an NR2A-containing NMDAR antagonist. These results suggest that the Induction of LTP by HFS in the dorsolateral striatum is NMDAR-dependent and requires NR2A-containing NMDARs, not NR2B-containing NMDARs.
Tong Zhang - One of the best experts on this subject based on the ideXlab platform.
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Role of phosphorylation of ERK in Induction and maintenance of LTP of the C-fiber evoked field potentials in spinal dorsal horn.
Journal of neuroscience research, 2006Co-Authors: Wen Jun Xin, Hong Wei Yang, Tong Zhang, Qing-juan Gong, Ying Zang, Xian-guo LiuAbstract: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 microM), 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.
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Diazepam inhibits the Induction and maintenance of LTP of C-fiber evoked field potentials in spinal dorsal horn of rats
Neuropharmacology, 2005Co-Authors: Hongmei Zhang, Tong Zhang, Li Jun Zhou, Yifan Han, Xian-guo LiuAbstract:Abstract The benzodiazepine diazepam impairs memory and long-term potentiation (LTP) in the hippocampus. Here, we investigate the effect of diazepam on LTP of C-fiber evoked field potentials in spinal dorsal horn, which is relevant to pathological pain. LTP of C-fiber evoked field potentials was recorded in the superficial layers of spinal dorsal horn in urethane-anesthetized Sprague–Dawley rats. Diazepam was applied locally at the recording spinal segments before and after LTP Induction by tetanic stimulation. We found (1) Diazepam completely blocked LTP Induction. (2) Diazepam and midazolam reversed spinal LTP, when applied at 30 min after LTP Induction and depressed but could not reverse spinal LTP, when applied at 3 h after LTP Induction. (3) Pretreatment with benzodiazepine receptor antagonist flumazenil or GABAA receptor antagonist bicuculline completely blocked the inhibitory effects of diazepam on spinal LTP. In contrast, when the inhibitory effect of diazepam was fully established, neither of these antagonists was capable of reversing the inhibition by diazepam. (4) Spinal application of the GABAA receptor agonist 3-amino-1-propanesulfonic acid (3-APSA) at a dose of 50 μg, produced a transient inhibition of spinal LTP. These results suggest that diazepam might prevent and depress spinal plastic change produced by noxious stimulation via activation of the GABAA–benzodiazepine receptor complex.
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Roles of CaMKII, PKA, and PKC in the Induction and Maintenance of LTP of C-Fiber-Evoked Field Potentials in Rat Spinal Dorsal Horn
Journal of neurophysiology, 2003Co-Authors: Hong Wei Yang, Hongmei Zhang, Wen Jun Xin, Tong Zhang, Li Jun Zhou, Xian-guo LiuAbstract:Long-term potentiation (LTP) of C-fiber-evoked field potentials in spinal dorsal horn may be relevant to hyperalgesia, an increased response to noxious stimulation. The mechanism underlying this form of synaptic plasticity is, however, still unclear. Considerable evidence has shown that calcium/calmodulin-dependent protein kinase II (CaMKII), protein kinase A (PKA), and protein kinase C (PKC) are important for LTP in hippocampus. In this study, the roles of these three protein kinases in the Induction and maintenance of LTP of C-fiber-evoked field potentials were evaluated by application of specific inhibitors of CaMKII (KN-93 and AIP), PKA (Rp-CPT-cAMPS), and PKC (chelerythrine and Go 6983) at the recording segments before and after LTP Induction in urethane-anesthetized Sprague-Dawley rats. We found both KN-93 and AIP, when applied at 30 min prior to tetanic stimulation, completely blocked LTP Induction. At 30 min after LTP Induction, KN-93 and AIP reversed LTP completely, and at 60 min after LTP Induction, they depressed spinal LTP in most rats tested. Three hours after LTP Induction, however, KN-93 or AIP did not affect the spinal LTP. Rp-CPT-cAMPS, chelerythrine, and Go 6983 blocked the spinal LTP when applied at 30 min before tetanic stimulation and reversed LTP completely at 15 min after LTP Induction. In contrast, at 30 min after LTP Induction, the drugs never affected the spinal LTP. These results suggest that activation of CaMKII, PKA, and PKC may be crucial for the Induction and the early-phase but not for the late-phase maintenance of the spinal LTP.
Roger Anwyl - One of the best experts on this subject based on the ideXlab platform.
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Beta-amyloid-mediated inhibition of NMDA receptor-dependent long-term potentiation Induction involves activation of microglia and stimulation of inducible nitric oxide synthase and superoxide.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2004Co-Authors: Qinwen Wang, Michael J. Rowan, Roger AnwylAbstract:The mechanisms underlying the inhibition of long-term potentiation (LTP) Induction by amyloid-peptide (A) were investigated in the medial perforant path of the rat and mouse dentate gyrus in vitro. Evidence is presented in this study that the A-mediated inhibition of LTP Induction involves activation of microglia and production of reactive oxygen and nitrogen species. In control slices, A strongly inhibited Induction of NMDA receptor-dependent (NMDAR-dependent) LTP, although not Induction of NMDAR-independent LTP or long-term depression (LTD). The inhibition of NMDAR-dependent LTP was prevented by minocycline, an agent that prevents activation of microglia. The involvement of inducible nitric oxide synthase (iNOS) was shown by the inability of A to inhibit LTP Induction in iNOS knock-out mice and also by the ability of two iNOS inhibitors, aminoguanidine and 1400W, to prevent the A-mediated inhibition of LTP Induction. The A-mediated inhibition of LTP Induction also was prevented by the superoxide scavenger superoxide dismutase applied together with catalase. Evidence for involvement of superoxide in the action of A on LTP Induction was shown by the ability of an inhibitor of NADPH oxidase to prevent the A-mediated inhibition of LTP Induction. The study thus provides evidence that the Amediated inhibition of LTP Induction involves an inflammatory-type reaction in which activation of microglia results in the production of nitric oxide and superoxide and thence possibly peroxynitrite, a highly reactive oxidant.
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Block of Long-Term Potentiation by Naturally Secreted and Synthetic Amyloid β-Peptide in Hippocampal Slices Is Mediated via Activation of the Kinases c-Jun N-Terminal Kinase, Cyclin-Dependent Kinase 5, and p38 Mitogen-Activated Protein Kinase as well
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2004Co-Authors: Qinwen Wang, Michael J. Rowan, Dominic M. Walsh, Dennis J. Selkoe, Roger AnwylAbstract:The mechanisms of action of human synthetic and naturally secreted cell-derived amyloid β-peptide (Aβ)1–42 on the Induction of long-term potentiation (LTP) were investigated in the medial perforant path to dentate granule cell synapses in hippocampal slices. Synthetic and cell-derived Aβ strongly inhibited high-frequency stimulation (HFS)-induced LTP at peak HFS and 1 hr after HFS. Cell-derived Aβ was much more potent than synthetic Aβ at inhibiting LTP Induction, with threshold concentrations of ∼1 and 100–200 nm, respectively. The involvement of various kinases in Aβ-mediated inhibition of LTP Induction was investigated by applying Aβ in the presence of inhibitors of these kinases. The c-Jun N-terminal kinase (JNK) inhibitor JNKI prevented the block of LTP Induction by both synthetic and cell-derived Aβ. The block of LTP induced by synthetic Aβ was also prevented by the JNK inhibitor anthra[1,9-cd]pyrazol-6(2H)-one, the cyclin-dependent kinase 5 (Cdk5) inhibitors butyrolactone and roscovitine, and the p38 MAP kinase (MAPK) inhibitor 4-(4-fluorophenyl)-2-(4-methylsulfonylphenyl)-5-(4-pyridyl)-1H-imidazole but not by the p42–p44 MAP kinase inhibitor 1,4-diamino-2,3-dicyano-1,4-bis(2-aminophenylthio)butadiene. The group I–group II metabotropic glutamate receptor (mGluR) antagonist 2S-2-amino-2-(1S,2S-2-carboxycyclopropyl-1-yl)-3-(xanth-9-yl)propanoic acid and the mGluR5 antagonist methyl-6-(phenylethynyl)pyridine prevented the block of LTP Induction by Aβ. However, theα7 nicotinic ACh receptor antagonist methylcaconatine did not prevent the inhibition of LTP Induction by Aβ. These studies provide evidence that the Aβ-mediated inhibition of LTP Induction involves stimulation of the kinases JNK, Cdk5, and p38 MAPK after the activation of both the Aβ receptor(s) and mGluR5.
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Endogenous acetylcholine lowers the threshold for long-term potentiation Induction in the CA1 area through muscarinic receptor activation: in vivo study.
The European journal of neuroscience, 2004Co-Authors: Saak V. Ovsepian, Roger Anwyl, Michael J. RowanAbstract:Little is known how synaptically released endogenous ACh affects hippocampal synaptic plasticity in vivo. Here, we examined the role of cholinergic drive in the regulation of the Induction of long-term potentiation (LTP) at basal dendrites in the CA1 area of the anaesthetized rat hippocampus. The non-subtype selective muscarinic acetylcholine receptor antagonist, scopolamine, (0.3 mg/kg, i.p.) inhibited the Induction of LTP by weak, but not strong, high frequency conditioning stimulation. A relatively M1 subtype-selective receptor antagonist, pirenzepine, (50 nmol/5 microL, i.c.v.) also inhibited LTP Induction by the weak protocol. As the medial septum (MS) is a major source of endogenous ACh in the hippocampus, we also examined the effect of high frequency pre-conditioning stimulation of the MS on LTP Induction. The pre-conditioning MS tetanus reduced the threshold for LTP Induction at basal synapses in a narrow time window. Such an effect of MS pre-conditioning was prevented by scopolamine, strong evidence of a direct MS control of LTP threshold through a mechanism dependent on muscarinic receptor activation. These results suggest that the cholinergic drive to the hippocampus is critically involved in the control of the LTP Induction threshold in vivo. To the extent that LTP mechanisms may underlie certain types of learning and memory, the septo-hippocampal cholinergic regulation of synaptic plasticity may constitute an important target for the treatment of cognitive disorders associated with ACh deficits.
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Mechanisms underlying the inhibition of long-term potentiation by preconditioning stimulation in the hippocampus in vitro.
Neuroscience, 2003Co-Authors: Barbara Gisabella, Michael J. Rowan, Roger AnwylAbstract:We have investigated the mechanisms underlying a form of metaplasticity, namely the inhibition by preconditioning stimulation of high frequency stimulation (HFS)-induced long-term potentiation (LTP) in the medial perforant path of the dentate gyrus. Preconditioning stimulation (weak 50 Hz) was found to inhibit subsequent LTP Induction if applied 10-20 min, but not 2 or 45 min, prior to the HFS. Preconditioning stimulation in the form of low frequency stimulation did not block LTP Induction. The inhibition of LTP was not caused by a reduction in N-methyl-D-aspartate receptor (NMDAR) transmission, as the preconditioning stimulation did not reduce isolated NMDAR-mediated EPSPs. The involvement of group I and group II metabotropic glutamate receptor (mGluR) activation in the inhibition of LTP was demonstrated by experiments in which the inhibition of LTP by the preconditioning stimulation was prevented by the presence of antagonists of group I or group II mGluR during the preconditioning stimulation. Moreover, group I and group II mGluR agonists directly inhibited subsequent LTP Induction. The involvement of NMDAR in the preconditioning stimulation was shown by the ability of an NMDAR antagonist to prevent the inhibition of LTP by the preconditioning stimulation. The preconditioning inhibition of LTP Induction was shown by the use of kinase inhibitors to involve activation of PKC and p38 MAP kinase, but not p42 MAP kinase or tyrosine kinase. We conclude that the preconditioning inhibition of LTP Induction is a complex process which involves activation of NMDAR, group I and group II mGluR, and intracellular cascades activating PKC and p38 MAP kinase.
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LTP Induction Dependent on Activation of Ni2+-Sensitive Voltage-Gated Calcium Channels, but not NMDA Receptors, in the Rat Dentate Gyrus In Vitro
Journal of neurophysiology, 1997Co-Authors: Yue Wang, Michael J. Rowan, Roger AnwylAbstract:Wang, Yue, Michael J. Rowan, and Roger Anwyl. LTP Induction dependent on activation of Ni2+-sensitive voltage-gated calcium channels, but not NMDA receptors, in the rat dentate gyrus in vitro. J. N...
Toshiya Manabe - One of the best experts on this subject based on the ideXlab platform.
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requirement of appropriate glutamate concentrations in the synaptic cleft for hippocampal LTP Induction
European Journal of Neuroscience, 2001Co-Authors: H Katagiri, Kohichi Tanaka, Toshiya ManabeAbstract:: Although glutamate transporters maintain low extracellular levels of the excitatory neurotransmitter glutamate in the nervous system, little is known about their roles in synaptic plasticity. Here, using knockout mice lacking GLT-1, that is the most abundant glial subtype of glutamate transporters, we showed that long-term potentiation (LTP) induced by tetanic stimulation in mutant mice was impaired in the hippocampal CA1 region. When tetanic stimulation was applied in the presence of low concentrations of an N-methyl-D-aspartate (NMDA) receptor antagonist, the impairment was overcome. Consistent with these results, the increased glutamate in the synaptic cleft of mutant mice preferentially activated NMDA receptors. Furthermore, analyses of mutant mice revealed that the magnitude of NMDA receptor-dependent transient synaptic potentiation during low-frequency stimulation depended on the concentration of glutamate in the synaptic cleft. These findings suggest that GLT-1 plays critical roles in LTP Induction, as well as in short-term potentiation, through regulation of extracellular levels of glutamate, which enables appropriate NMDA receptor activation.
