Biomedical subjects

R Anwyl

Publications and source records attributed to R Anwyl.

At least 55 records · Page 3Linked to original sources

PubMed1997

Block of theta-burst-induced long-term potentiation by (1S,3S)-1-aminocyclopentane-1,3-dicarboxylic acid: further evidence against long-term potentiation as a model for learning.

It has been previously reported that block of high-frequency stimulation-induced long-term potentiation of synaptic transmission in the hippocampus does not necessarily lead to impairment of spatial learning. Here we show that (1S,3S)-1-aminocyclopentane-1,3-dicarboxylic acid, an agonist at group II metabotropic glutamate receptors, completely blocked long-term potentiation induced by a theta-burst type of stimulation protocol (five pulses at 75 Hz per train, 200 ms inter-train interval) in the CA1 region in vivo. The drug did not significantly affect synaptic responses during each train whereas inter-train facilitation of excitatory postsynaptic potentials was slightly reduced. It also produced a large reduction in paired-pulse facilitation (50 ms inter-stimulus interval), possibly indicating that an increase in inhibition might be involved in the block of long-term potentiation. The drug dose used (5 microliters of a 10 mM solution i.c.v.) was half the dose which inhibited high-frequency stimulation-induced long-term potentiation in earlier experiments but which did not prevent learning of spatial tasks. We conclude that long-term potentiation induced by a more physiological stimulation protocol which uses theta-like inter-train intervals does not appear to accurately model the synaptic changes which are believed to occur during learning either.

Action Potentials↗

PubMed1997

Evidence for involvement of the neuronal isoform of nitric oxide synthase during induction of long-term potentiation and long-term depression in the rat dentate gyrus in vitro.

The possible role of nitric oxide in the induction of long-term potentiation and long-term depression of field excitatory postsynaptic potentials in the dentate gyrus of the hippocampal slice has been investigated, in the rat, using two novel nitric oxide synthase inhibitors, 1-(2-trifluoromethylphenyl)imidazole, which is selective for the neuronal isoform in vitro, and 3-bromo-7-nitro-indazole. Long-term potentiation was induced by a series of high-frequency trains, and long-term depression was induced by prolonged low-frequency stimulation at 1 Hz. The induction of long-term potentiation was inhibited by both 1-(2-trifluoromethylphenyl)imidazole and 3-bromo-7-nitro-indazole at concentrations which did not alter the amplitude of the test excitatory postsynaptic potential. The inhibitory effect of 1-(2-trifluoromethylphenyl)imidazole on the induction of long-term potentiation was prevented by pretreatment with L-arginine, the substrate amino acid used by nitric oxide synthase for nitric oxide production. The induction of long-term depression was inhibited by both 3-bromo-7-nitro-indazole and 1-(2-trifluoromethylphenyl)imidazole at concentrations which did not affect the test excitatory postsynaptic potential. The inhibitory effect of 1-(2-trifluoromethylphenyl)imidazole was prevented by pretreatment with L-arginine. The present experiments provide strong support for the involvement of the neuronal isoform of nitric oxide synthase in the induction of long-term potentation and long-term depression.

Animals↗

PubMed1997

Induction of LTD in the dentate gyrus in vitro is NMDA receptor independent, but dependent on Ca2+ influx via low-voltage-activated Ca2+ channels and release of Ca2+ from intracellular stores.

The mechanisms of the induction of long-term depression (LTD) of field excitatory postsynaptic potentials (EPSPs) and whole cell patch-clamped excitatory postsynaptic currents (EPSCs) were studied in the dentate gyrus of the rat hippocampus. LTD of field EPSPs measuring 40% of control at 30 min poststimulation was induced by low-frequency stimulation consisting of 900 pulses at 1 Hz. LTD of EPSCs measuring 37% of control was induced by a pairing procedure consisting of 60 pulses at 1 Hz applied under voltage clamp at a holding potential of -40 mV. The induction of LTD of field EPSPs was dependent on an influx of extracellular calcium, being reduced in a low-Ca2+ (0.8 mM) medium. However, substantial LTD (26%) was still induced in such a medium, demonstrating the relatively low sensitivity of LTD induction to the level of extracellular Ca2+. A high concentration of the N-methyl-D-aspartate receptor antagonist D(-)-2-amino-5-phosphonopentanoic acid (D-AP5) (100 microM) did not significantly inhibit the induction of LTD of EPSCs evoked by the intracellular pairing procedure. D-AP5 partially reduced the magnitude of LTD of field EPSPs, but substantial LTD was still induced in the presence of AP5. The induction of LTD was strongly inhibited by Ni2+ (50 microM) but not by nifedipine (10 microM), indicating that Ca2+ influx via T-type, but not L-type, Ca2+ channels is required for the induction of LTD. The induction of LTD was strongly inhibited by thapsigargin, an agent known to deplete intracellular Ca2+ stores. The induction of LTD, but not long-term potentiation (LTP), was also strongly inhibited by ruthenium red, an agent known to block the ryanodine receptors located on intracellular Ca2+ stores. These results demonstrate that Ca2+ release from intracellular Ca2+ stores is required for the induction of LTD, but not LTP. The results of the present experiments suggest that the induction of LTD involves the entry of Ca2+ via low-voltage-activated voltage-gated Ca2+ channels followed by release of Ca2+ from intracellular ryanodine-receptor-sensitive Ca2+ stores.

Animals↗

PubMed1997

Conditions for the induction of long-term potentiation and long-term depression by conjunctive pairing in the dentate gyrus in vitro.

Conditions for the induction of long-term potentiation and long-term depression by conjunctive pairing in the dentate gyrus in vitro. J. Neurophysiol. 78: 2569-2573, 1997. The conditions under which long-term potentiation (LTP) and long-term depression (LTD) of excitatory postsynaptic currents were induced by the conjunctive pairing-type protocol of afferent stimulation and postsynaptic depolarization were studied in the medial perforant pathway-granule cell synapse of the dentate gyrus in vitro. The conjunctive pairing of 1-Hz afferent stimulation and steady state postsynaptic depolarization to 0 mV did not induce LTP or LTD. Inhibition of LTD induction with a phosphatase inhibitor or ruthenium red resulted in induction of LTP after the conjunctive pairing. Such LTP induction was N-methyl--aspartate dependent. Conversely, inhibition of LTP induction with a kinase inhibitor resulted in LTD induction after the conjunctive pairing. Thus the failure to induce LTP or LTD with the pairing protocol involving depolarization to 0 mV membrane potential was due to simultaneous activation of intracellular processes that generate the induction of LTP and LTD. Increasing the frequency of afferent stimulation to 200 Hz, even for just eight stimuli, resulted in LTP induction. The studies show that two factors govern the induction of LTP/LTD, membrane potential and frequency of afferent stimulation, with either increased depolarization or increased afferent stimulation favoring LTP induction.

2-Amino-5-phosphonovalerate↗

PubMed1997

LTP induction dependent on activation of Ni2+-sensitive voltage-gated calcium channels, but not NMDA receptors, in the rat dentate gyrus in vitro.

LTP induction dependent on activation of Ni2+-sensitive voltage-gated calcium channels, but not NMDA receptors, in the rat dentate gyrus in vitro. J. Neurophysiol. 78: 2574-2581, 1997. A N-methyl--aspartate receptor (NMDAR)-independent long-term potentiation (LTP) has been investigated in the dentate gyrus of the hippocampus in vitro in the presence of the NMDAR antagonist, -2-amino-phosphonopentanoate (50-100 mu M), at a concentration that completely blocked NMDAR-mediated excitatory postsynaptic currents (EPSCs). LTP of patch-clamped EPSCs was induced by pairing low-frequency evoked EPSCs (1 Hz) with depolarizing voltage pulses designed to predominately open low-voltage-activated (LVA) Ca2+ channels. Voltage pulses alone induced only a short-term potentiation. The LTP was blocked by intracellular application of the rapid Ca2+ chelator bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid, demonstrating that a rise in intracellular Ca2+ is required for the NMDAR-independent LTP induction. The NMDAR-independent LTP induction also was blocked by Ni2+ at a low extracellular concentration (50 mu M), which is known to strongly block LVA Ca2+ channels. However, Ni2+ did not inhibit the NMDAR-dependent LTP induced by high-frequency stimulation (HFS). The NMDAR-independent LTP induction was not blocked by high concentrations of the L-type Ca2+ channel blocker nifedipine (10 mu M). The NMDAR-independent LTP was inhibited by the metabotropic glutamate receptor ligand (+)-alpha-methyl-4-carboxyphenylglycine. These experiments demonstrate the presence of a NMDAR-independent LTP induced by Ca2+ influx via Ni2+-sensitive, nifedipine-insensitive voltage-gated Ca2+ channels, probably LVA Ca2+ channels. Induction of the NMDAR-independent LTP was inhibited by prior induction of HFS-induced NMDAR-dependent LTP, demonstrating that although the NMDAR-dependent and NMDAR-independent LTP use a different Ca2+ channel for Ca2+ influx, they share a common intracellular pathway.

2-Amino-5-phosphonovalerate↗

PubMed1996

beta-Amyloid produces a delayed NMDA receptor-dependent reduction in synaptic transmission in rat hippocampus.

The delayed effect of in vivo injection of beta-amyloid on glutamatergic synaptic transmission was investigated in the rat hippocampus. The amplitude of field excitatory postsynaptic potentials recorded in the CA1 region of awake rats was reduced 24 h after the injection of beta-amyloid (1-40) (0.4 or 3.5 nmol i.c.v.). The effect lasted for at least 5 days and was prevented by treatment with the N-methyl-D-aspartate (NMDA) receptor antagonist CPP (7 mg kg-1 x 2, i.p.). Similar results were obtained ex vivo in the dentate gyrus. There was no change in the ability to induce long-term potentiation. These results provide direct evidence that beta-amyloid produced a delayed reduction in the function of glutamatergic synapses, probably as a result of an initial over-activation of the NMDA receptor-mediated component of transmission.

Amyloid beta-Peptides↗

PubMed1996

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

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.

2-Amino-5-phosphonovalerate↗

PubMed1996

Metabotropic glutamate receptor dependent EPSP and EPSP-spike potentiation in area CA1 of the submerged rat hippocampal slice.

1. We reexamined the important areas of conflict in (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid [(1S,3R)-ACPD]-induced potentiation of the field excitatory postsynaptic potential (EPSP) and, for the first time, investigated the role of mGluRs in EPSP-spike (E-S) coupling. 2. (1S,3R)-ACPD (10 microM) bath applied for 20 min consistently induced a long-lasting potentiation of the dendritic EPSP in area CA1 of submerged rat hippocampal slices, which was considerably faster in onset than described previously. 3. This effect was not associated with any change in presynaptic fiber volley but was dependent on both an intact CA3 connection, because removal of area CA3 blocked (1S,3R)-ACPD-induced potentiation, and also on functional N-methyl-D-aspartate (NMDA) receptors, because (1S,3R)-ACPD-induced potentiation was blocked by inclusion of the NMDA receptor antagonist D(-)-2-amino-5-phosphonopentanoic acid (AP5; 50 microM). 4. (1S,3R)-ACPD induced a long-lasting potentiation of the population spike (PS) amplitude that was consistently larger than that of the EPSP measured in the cell body area. This EPSP-PS (E-S) potentiation was blocked by inclusion of the gamma-aminobuturic acid-A (GABAA) receptor antagonist, picrotoxin (50 microM). 5. E-S potentiation induced by high-frequency stimulation (HFS), which was of the same magnitude as that induced by (1S,3R)-ACPD, was blocked by the mGluR-selective antagonist (+)-alpha-methyl-4-carboxyphenylglycine (+MCPG; 250 microM). +MCPG also blocked HFS-induced long-term potentiation (LTP) of the EPSP measured in the cell body. 6. These results suggest that (1S,3R)-ACPD-induced potentiation is NMDA receptor dependent, contrary to some previous findings, and provide further evidence that both synaptic and E-S potentiation induced by (1S,3R)-ACPD share common mechanisms of expression with HFS-induced LTP. The data emphasize the important role of mGluRs in induction of EPSP LTP and E-S potentiation.

Animals↗

PubMed1996

The selective neuronal NO synthase inhibitor 7-nitro-indazole blocks both long-term potentiation and depotentiation of field EPSPs in rat hippocampal CA1 in vivo.

The membrane-permeant gas NO is a putative intercellular messenger that has been proposed on the basis of previous in vitro studies to be involved in synaptic plasticity, especially the induction of long-term potentiation (LTP) of excitatory synaptic transmission in the hippocampus and cortex. In the present study, the role of NO in synaptic plasticity has been investigated in vivo. In particular, the action of the novel and selective neuronal NO synthase (nNOS) inhibitor 7-nitro-indazole (7-NI) has been investigated on the induction of LTP and depotentiation (DP) of field EPSPs in CA1 of the hippocampus in vivo. Unlike previously studied nonselective NOS inhibitors, 7-NI does not increase arterial blood pressure. In vehicle-injected rats, high-frequency stimulation consisting of a series of trains at 200 Hz induced LTP. However, LTP induction was strongly inhibited in 7-NI (30 mg/kg, i.p.)-treated animals. The inhibitory effect of 7-NI on the induction of LTP was prevented by pretreatment with L-arginine, the substrate amino acid used by NOS. In control animals, low-frequency stimulation consisting of 900 stimuli at 10 Hz induced DP of previously established LTP, whereas in 7-HI-treated animals only a short-term depression was induced. This effect of 7-NI also was prevented by D-arginine. The LTP and DP induced in control animals in this study were NMDA receptor-dependent, the NMDA receptor antagonist 3-(R,S)-2-carboxypiperazin-4-yl-propyl-1- phosphonic acid inhibiting the induction of both forms of synaptic plasticity. The present experiments are the first to demonstrate that an NOS inhibitor blocks the induction of the synaptic component of LTP and DP in vivo and, therefore, these results strengthen evidence that the production of NO is necessary for the induction of LTP and DP.

Animals↗

PubMed1995

The azapirone metabolite 1-(2-pyrimidinyl)piperazine depresses excitatory synaptic transmission in the hippocampus of the alert rat via 5-HT1A receptors.

The effects of acute and repeated treatment with 1-(2-pyrimidinyl)piperazine (1-PP), a metabolite of the 5-HT1A receptor ligand azapirones, were investigated on hippocampal excitatory synaptic transmission. Recordings of the electrically evoked field population excitatory post-synaptic potentials (e.p.s.p.s.) were carried out in the stratum radiatum of the CA1 region of the dorsal hippocampus of alert rats. Acute i.p. administration of 1-PP transiently reduced the e.p.s.p. amplitude in a dose-dependent (0.25-1 mg/kg) manner. This effect was blocked by the 5-HT1A receptor antagonists spiroxatrine (1 mg/kg) and MDL 73005EF (8-[2-(2,3-dihydro-1,4-benzodioxin-2-yl methylaminoethyl]-8-azaspirol[4,5]decane-7,9-dione methyl sulphonate, 2 mg/kg). Intrahippocampal administration of 1-PP (5 microg) evoked a transient reduction of the e.p.s.p. amplitude which was similar to that obtained with 5-HT (10 microg). 1-PP (0.25 mg/kg per day) administered for 9 days produced a gradual reduction in the daily pre-injection baseline e.p.s.p. amplitude coupled with a decrease in the acute response to the drug. The chronic baseline reduction was transiently reversed by spiroxatrine and full recovery to pretreatment levels was observed 4 days after the last 1-PP dose. These findings indicate that the previously reported reduction in the e.p.s.p. produced by the azapirone group of 5-HT1A receptor ligands may be mediated in part by their metabolite 1-PP through activation of 5-HT1A receptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1995

beta-Amyloid selectively augments NMDA receptor-mediated synaptic transmission in rat hippocampus.

The effect of beta-amyloid on alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptor-mediated glutamatergic excitatory postsynaptic currents measured with whole-cell voltage-clamp techniques, was investigated in the rat dentate gyrus in vitro. Application of beta-amyloid (1-40) by extracellular perfusion (200 nM) or intracellularly via the recording pipette (100 nM) resulted in a gradual enhancement of the NMDA receptor-mediated synaptic currents which did not reverse on washout. Basal AMPA receptor-mediated transmission, resting membrane potential or input resistance of the granule cells did not change. These results provide direct evidence that beta-amyloid selectively interacts with the potentially neurotoxic NMDA receptor via a postsynaptic site. It is proposed that this action may help explain the synaptic changes seen in Alzheimer's disease.

Amyloid beta-Peptides↗

PubMed1995

beta-Amyloid-(1-40) increases long-term potentiation in rat hippocampus in vitro.

The effect of beta-amyloid-(1-40) was investigated on long-term potentiation of glutamatergic excitatory postsynaptic field potentials recorded in the inner molecular layer in the rat dentate gyrus in vitro. In the presence of 200 nM beta-amyloid-(1-40) there was an increase in long-term potentiation of 51%. Basal synaptic transmission was not affected. These results provide direct evidence that a relatively low concentration of beta-amyloid-(1-40) increases synaptic plasticity.

Amyloid beta-Peptides↗

PubMed1995

(RS)-alpha-Methyl-4-carboxyphenylglycine inhibits long-term potentiation only following the application of low frequency stimulation in the rat dentate gyrus in vitro.

The effect of the metabotropic glutamate receptor (mGluR) antagonist (RS)-alpha-methyl-4-carboxyphenylglycine (MCPG) was investigated on the induction of long-term potentiation (LTP) of alpha-amino-3-hydroxy-5- methyl-4-isoxazoleproprionate receptor-mediated excitatory postsynaptic currents (epscs) recorded from dentate granule cells in response to presynaptic stimulation of the associational/commissural pathway of the rat dentate gyrus in vitro. MCPG (500 microM, 60 min) did not inhibit the induction of LTP of epscs induced by high frequency stimulation (HFS) at sites which had received only test stimulation (0.05/s) preceding the HFS. MCPG did, however, block the induction of LTP of epscs elicited by HFS if the HFS was preceded by the induction of long-term depression elicited by low frequency stimulation (5 Hz for 3 min). After such low frequency stimulation, HFS induced only a short-term potentiation lasting up to a maximum of 10 min in the presence of MCPG.

Animals↗

PubMed1995

Metabotropic glutamate receptor-induced homosynaptic long-term depression and depotentiation in the dentate gyrus of the rat hippocampus in vitro.

We have investigated the role of metabotropic glutamate receptors (mGluR) in the induction of homosynaptic long-term depression (LTD) and depotentiation (DP) in the dentate gyrus of the adult rat. Perfusion of the mGluR agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) for a prolonged period (20 min) induced long-term depression (LTD) of field excitatory postsynaptic field potentials (epsps) from the baseline level and also depotentiation (DP) from the long-term potentiated level. Both the ACPD-and the low frequency stimulation (LFS)-induced LTD and DP were inhibited in the presence of the mGluR antagonist (+)-alpha-methyl-4-carboxyphenylglycine (MCPG), demonstrating the necessity for the activation of metabotropic glutamate receptors in the induction of LTD/DP. The LFS and ACPD-induced LTD were independent of the activation of N-methyl-D-aspartate (NMDA) receptors, as they were not blocked by the NMDA receptor antagonist D-2-amino-5-phophonopentanoate (AP5).

Animals↗

PubMed1995

Dantrolene inhibits long-term depression and depotentiation of synaptic transmission in the rat dentate gyrus.

The involvement of Ca release from intracellular stores in the induction of long-term depression and depotentiation of excitatory synaptic transmission was investigated in the rat dentate gyrus using dantrolene, an agent known to block Ca release via the ryanodine receptor. In control slices, low-frequency stimulation (1 Hz for 15 min) induced robust long-term depression of baseline field excitatory postsynaptic potentials and depotentiation of previously established long-term potentiation. Dantrolene (50 microM) was found to block completely both long-term depression of baseline responses and depotentiation. Moreover, long-term potentiation induced by high-frequency stimulation was enhanced in the presence of dantrolene.

Animals↗

PubMed1995

Potentiation of N-methyl-D-aspartate-receptor-mediated currents detected using the excised patch technique in the hippocampal dentate gyrus.

The excised patch mode of the patch-clamp technique has been used to record isolated patch N-methyl-D-aspartate-receptor-mediated currents (patch NMDA-receptor-currents) evoked by electrical stimulation in the dentate gyrus of the hippocampal slice. The patch NMDA-receptor-currents were recorded by placing a patch of membrane isolated from the cell body in the inner molecular layer of the dentate gyrus and applying stimulation to the proximal commissural/associational pathway. The patch NMDA-receptor-currents, recorded at +40 mV in the presence of AMPA-receptor and GABAA-receptor antagonists, consisted of two to six summated unitary openings of NMDA-receptor channels, lasting several hundred milliseconds. Tetanic pathway stimulation evoked a rapid increase in the amplitude of the patch NMDA-receptor-currents which lasted for a period of at least 20 min following the tetanus. The study suggests that the potentiation of the patch NMDA-receptor-currents is due to either an increase in transmitter release, or alternatively, to the release of an extracellular messenger which directly enhances NMDA-receptor responsiveness.

Animals↗

PubMed1995

Tetanically induced LTP involves a similar increase in the AMPA and NMDA receptor components of the excitatory postsynaptic current: investigations of the involvement of mGlu receptors.

Whole-cell patch-clamp recordings of evoked excitatory postsynaptic currents (EPSCs) were made from granule cells of the rat dentate gyrus in vitro. Tetanic stimulation in control media evoked a statistically identical long-term potentiation (LTP) of both the AMPA and NMDA receptor-mediated components of the dual component EPSC (AM-PAR and NMDAR EPSCs), as shown by a similar percentage increase in both components when measured at a holding potential of -30 mV, and also by an identical time course of the pre- and post-LTP induced EPSC at -30 mV and -70 mV. Application of the selective metabotropic glutamate receptor (mGluR) agonist 1S,3R-ACPD induced a transient depression followed by a rapid onset LTP of both the AMPAR and the NMDAR components of the dual component EPSC. The ACPD- and tetanically induced LTP of the AMPAR EPSC was NMDAR dependent, being abolished by the NMDAR antagonist AP5. Tetanic stimulation, and application of ACPD, also induced a relatively rapid onset LTP of the pharmacologically isolated NMDAR EPSC. Such tetanically and ACPD-induced LTP of the isolated NMDAR EPSC was also dependent on NMDAR activation, being strongly inhibited by AP5. The tetanically and the ACPD-induced LTP of the NMDAR EPSC were dependent on protein kinase C (PKC) stimulation, being strongly inhibited by the PKC inhibitor PKCI (19-31). The studies suggest that coactivation of the mGluR and NMDAR are required for induction of LTP of both the AMPAR- and NMDAR-mediated synaptic transmission. Moreover, LTP of the NMDAR-mediated synaptic transmission appears to be dependent on coincident activation of the NMDAR and mGluR.

Animals↗

PubMed1994

Synaptic plasticity. A molecular switch for memory.

The metabotropic glutamate receptor controls a molecular switch that, when activated, generates a conditioned state essential for the induction of long-term potentiation of synaptic transmission in the hippocampus.

Animals↗