Biomedical subjects

K G Reymann

Publications and source records attributed to K G Reymann.

At least 91 records · Page 5Linked to original sources

PubMed1994

(RS)-alpha-methyl-4-carboxyphenylglycine (MCPG) does not block theta burst-induced long-term potentiation in area CA1 of rat hippocampal slices.

We have used the selective metabotropic glutamate receptor antagonist (RS)-alpha-methyl-4-carboxyphenylglycine (MCPG) to investigate in the CA1 hippocampal subregion in vitro whether coactivation of N-methyl-D-aspartate (NMDA) and metabotropic glutamate receptors is necessary for the induction of long-term potentiation (LTP) when LTP is induced by theta burst stimulation (TBS). When MCPG (500 microM) was bath applied 14-30 min prior to a triple high-frequency tetanization (100 Hz, 1 s) and washed out immediately afterwards the potentiation of the extracellularly recorded field potentials decayed gradually to baseline (P < 0.05) over 2-3 h. However, when MCPG was applied in the same manner before a triple TBS (10 bursts at 5 Hz, 100 Hz within the bursts) the resulting potentiation remained stable for at least 4 h. MCPG had no effect on baseline synaptic transmission or post-tetanic potentiation. These results demonstrate a clear difference in the mechanisms underlying these two different forms of LTP.

Animals↗

PubMed1994

(R,S)-alpha-methyl-4-carboxyphenylglycine (MCPG) blocks spatial learning in rats and long-term potentiation in the dentate gyrus in vivo.

Recently, it was demonstrated by the use of the competitive and selective antagonist (R,S)-alpha-methyl-4-carboxyphenylglycine (MCPG) that metabotropic glutamate receptor (mGluR) activation is required to induce long-term potentiation (LTP) in the hippocampus. Accordingly, we investigated whether MCPG also inhibits spatial learning. Rats were trained on a spatial alternation task in a Y-maze with footshock reinforcement, and MCPG (0.0208 mg) was injected intracerebroventricularly prior to training and/or retention test. Animals injected pre-training are clearly impaired in retention, whereas preretention application was without effect. A state dependency could be excluded. Additionally, MCPG at the same concentration completely blocks a potentiation at perforant path/dentate gyrus synapses in vivo. These results strongly implicate a role of mGluRs in spatial learning and LTP.

Animals↗

PubMed1994

Hippocampal long-term potentiation in vivo induces translocation of protein kinase C gamma.

The possible involvement of the Ca(2+)-dependent protein kinase C (PKC) isoenzymes alpha/beta and gamma in mechanisms of long-term potentiation (LTP) was investigated after tetanic stimulation of the perforant path in vivo. Brief tetanic stimulation of the perforant path resulted in a 150% increase in population spike amplitude recorded from the dentate gyrus synapses in response to test stimuli 5 and 10 min after tetanization. Immunoblot analysis of PKC immunoreactivity in cytosolic and membrane fractions revealed a LTP-induced translocation of gamma PKC but not alpha/beta PKC into the cytosol in dentate gyrus but also in the other ipsilateral hippocampal regions. These data suggest different physiological roles of Ca(2+)-dependent PKC isoenzymes in activity-dependent synaptic plasticity.

Animals↗

PubMed1994

2,3-diphosphoglyceric acid blocks long-term potentiation of excitatory postsynaptic currents in hippocampal CA1 neurons of the rat.

The dependence of long-term potentiation on an intact inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] metabolism was investigated with the whole-cell voltage-clamp method in the CA1 region of hippocampal slices. The intracellular application of 2,3-diphosphoglyceric acid (1 mM), an inhibitor of the Ins(1,4,5)P3 5-phosphatase and of Ins(1,4,5)P3 3-kinase eliminated the potentiation of postsynaptic currents in pyramidal cells 30 min after paired pre- and postsynaptic activation. These data suggest a possible role of postsynaptic inositol 1,4-bisphosphate and/or inositol 1,3,4,5-tetra-kisphosphate in synaptic plasticity.

2,3-Diphosphoglycerate↗

PubMed1994

The metabotropic glutamate receptor antagonist (+)-alpha-methyl-4-carboxyphenylglycine protects hippocampal CA1 neurons of the rat from in vitro hypoxia/hypoglycemia.

The ability of the selective metabotropic glutamate receptor (mGluR) antagonist alpha-methyl-4-carboxyphenylglycine (MCPG) to protect hippocampal CA1 neurons from a hypoxic/hypoglycemic injury was examined. Rat hippocampal slices were exposed to a 4 min hypoxia/hypoglycemia, and the recovery of evoked population spikes was monitored. 500 microM (+)-MCPG exhibited a statistically significant protective effect, whereas the (-)-isomer was ineffective. These data suggest that MCPG-sensitive mGluRs may contribute to hypoxia/hypoglycemia-induced injury in rat hippocampal slices.

Animals↗

PubMed1994

LTP in hippocampal CA1 of urethane-narcotized rats requires stronger tetanization parameters.

Rats with chronically implanted electrodes in the hippocampal CA1 region were tested in their capacity to express and maintain long-term potentiation (LTP) of the population spike (PS) or of the field excitatory postsynaptic potential (fEPSP). Two different states were compared: a) freely moving animals; b) urethane-anesthetized animals (1 g/kg, IP). We found that a short, high-frequency tetanus (six bursts of 15 pulses; 200 Hz; double-pulse width; interburst interval 10 s) increased PS amplitudes and fEPSP slopes up to 300% in response to test stimuli in double-pulse width; interburst interval 10 s) increased PS amplitudes and fEPSP slopes up to 300% in response to test stimuli in the awake rat. The PS amplitude slowly decreased in time, returning to baseline levels 4 h post-tetanically, whereas the fEPSP slope remained at higher values for 24 h. Urethane injection reduced the fEPSP slope and abolished the PS to normal test pulses. We thus increased the strength of the test stimuli until we again recorded magnitudes of PSs and fEPSPs comparable to those in the awake animal. In conjunction with these stronger stimuli, tetanus-induced LTP was elicited that for the PS was increased in magnitude and prolonged in duration compared to the untreated control group. Although, stronger tetanic stimuli were applied to the narcotized fEPSP group too, no difference was found compared to controls. These results suggest that urethane narcosis influences the sensitivity of CA1 neurons to express LTP. Stronger stimulation was required to induce and maintain a long-lasting potentiation of the fEPSP slope and PS amplitude.

Animals↗

PubMed1994

Cholecystokinin (CCK-8S) prolongs 'unsaturated' theta-pulse induced long-term potentiation in rat hippocampal CA1 in vitro.

The effects of bath-applied sulphated cholecystokinin octapeptide (CCK-8S; 500 nM) and the selective CCKB receptor antagonist PD 135158 (1 microM) on the induction and maintenance of an 'unsaturated' long-term potentiation (LTP) were examined using recordings of field excitatory postsynaptic potentials (fEPSP) and population spikes (PS) in the hippocampal CA1 region of the rat. LTP was induced by a single theta-pulse stimulation (10 pulses at 7 Hz) of the Schaffer collateral-commissural pathway. CCK-8S had minor effects on the induction of LTP but substantially prolonged LTP of both fEPSP and PS from about 1 to at least 3 h. The antagonist PD 135158 had no influence on the induction of potentiation of fEPSP slope, but decreased the potentiation of PS amplitude. The results support the view that CCK-8S may facilitate long-term changes in glutamatergic synaptic transmission of the hippocampus, such as LTP.

Animals↗

PubMed1993

(1S, 3R)-ACPD protects synaptic transmission from hypoxia in hippocampal slices.

The influence of (1S, 3R)-1-aminocyclopentane-1,3-dicarboxylic acid [(1S, 3R)-ACPD], an agonist of the metabotropic glutamate receptor (mGluR), on recovery from in vitro hypoxia was investigated. Transverse hippocampal slices were exposed to a severe hypoxia, and the recovery of field excitatory postsynaptic potentials (fEPSPs) of CA1 neurons was monitored 1 hr after reoxygenation. If 20 microM (1S, 3R)-ACPD was present during hypoxia, the recovery of the fEPSPs was significantly higher compared to controls. This protective effect was not observed, when the mGluR-antagonist L-2-amino-3-phosphonopropionate (L-AP3, 300 microM) was coapplied with (1S, 3R)-ACPD.

Alanine↗

PubMed1993

An antagonist of glutamate metabotropic receptors, (RS)-alpha-methyl-4-carboxyphenylglycine, prevents the LTP-related increase in postsynaptic AMPA sensitivity in hippocampal slices.

(RS)-alpha-methyl-4-carboxyphenylglycine (MCPG), a compound which selectively antagonizes metabotropic glutamate receptors (mGlu-R), presents the LTP of field excitatory postsynaptic potentials (fEPSP) as well as the tetanus-induced increase in AMPA-evoked responses (fPRs) in the CA1 region of hippocampal slices. This effects of MCPG provide evidence for the involvement of mGlu-Rs in mechanisms underlying the postsynaptic maintenance of LTP, which appears to be mediated, at least partially, by an increase in sensitivity and/or number of postsynaptic AMPA receptors.

Animals↗

PubMed1993

Simultaneous local pressure microejection of excitatory amino acids and field potential recording with a single micropipette in the hippocampal slice.

The ability to use the same micropipette for simultaneous pressure microejection and field potential recording ('spot pressure electrode') is described. This approach allows the use of a single electrode to record both field responses to pressure microejection of drugs (fPR) and synaptically evoked field excitatory postsynaptic potentials (fEPSP). To demonstrate this, the glutamate receptor agonists alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA, 100-300 microM) and N-methyl-D-aspartate (NMDA, 1 mM) were used. Both AMPA- and NMDA-evoked fPRs exhibited properties of postsynaptic responses. Thus, they were not significantly altered by tetrodotoxin (TTX, 0.5-1 microM), but were completely and reversibly blocked by an antagonist of AMPA/kainate receptors, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 20 microM) and D-2-amino-5-phosphonopentanoic acid (AP5, 20 microM), respectively. The responses to micropressure-ejected AMPA were more stable and probably restricted to a smaller locus than responses to iontophoretic AMPA ejection. Additionally, the AMPA and NMDA contained in the pipette (up to 500 microM) did not influence the fEPSP recorded with this pipette. Our results suggest that this method might be a useful experimental tool for studying the local effects of excitatory amino acids and other compounds.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1993

Co-activation of metabotropic glutamate and N-methyl-D-aspartate receptors is involved in mechanisms of long-term potentiation maintenance in rat hippocampal CA1 neurons.

Slices of hippocampal area CA1 in the rat were employed to test the hypothesis that the activation of metabotropic glutamate receptors during tetanization is necessary for the late maintenance of long-term potentiation. If the metabotropic glutamate receptor antagonist L-2-amino-3-phosphonopropionate was present during tetanization, post-tetanic and early long-term potentiation of the population spike as well as field excitatory postsynaptic potential developed almost normally. However, 100 min after tetanization, long-term potentiation of the field excitatory postsynaptic potential decreased in an irreversible manner. The same concentration of D-2-amino-3-phosphonopropionate was ineffective. If L-2-amino-3-phosphonopropionate was applied 120 min after tetanization, it did not influence long-term potentiation. The presence of the metabotropic glutamate receptor agonist trans-D,L-1-aminocyclopentane-1,3-dicarboxylic acid during tetanization weakly enhanced the slope of field excitatory postsynaptic potential long-term potentiation. The influence of L-2-amino-3-phosphonopropionate and D,L-1-aminocyclopentane-1,3-dicarboxylic acid on ionotropic glutamate receptors was studied using whole-cell voltage-clamp and pressure application techniques. No effect of L-2-amino-3-phosphonopropionate on either early or late components of excitatory postsynaptic currents could be detected at the concentration used to block long-term potentiation. It is therefore unlikely that the effect of L-2-amino-3-phosphonopropionate on long-term potentiation is due to an interaction with N-methyl-D-aspartate receptors or alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors. However, bath-applied 1S,3R-D,L-1-aminocyclopentane-1,3-dicarboxylic acid facilitated the N-methyl-D-aspartate-induced depolarization in response to N-methyl-D-aspartate pressure application in a reversible manner. These data suggest that besides the involvement of N-methyl-D-aspartate receptors the activation of a 2-amino-3-phosphonopropionate-sensitive metabotropic glutamate receptors during or immediately after tetanization is necessary for subsequent mechanisms responsible for the maintenance of long-term potentiation. A link between metabotropic glutamate receptors and protein kinase C activation during long-term potentiation is discussed considering the similar time course of long-term potentiation blockade after application of L-2-amino-3-phosphonopropionate and protein kinase C inhibitors.

Alanine↗

PubMed1993

Protein kinase A inhibitors prevent the maintenance of hippocampal long-term potentiation.

The possible involvement of cAMP-dependent protein kinase A (PKA) in mechanisms of long-term potentiation of the Schaffer collateral-commissural input of rat CA1 neurones was investigated using several inhibitors in vitro. If 10 microM H-8, 100 nM KT5720 or 50 microM Rp-cAMPs was applied to the bath before a triple 100 Hz/0.5 s tetanization, post-tetanic and short-term potentiation developed almost normally. However, from about 3 h after tetanization the long-term potentiation (LTP) of the field-EPSP declined with respect to the control in an irreversible manner. These data suggest that besides protein kinase C the synergistic activation of PKA is necessary for the maintenance of LTP.

Animals↗

PubMed1992

Effects of philanthotoxin-343 on CA1 pyramidal neurons of rat hippocampus in vitro.

A synthetic analog of philanthotoxin-433, philanthotoxin-343 (PhTX-343), was tested in hippocampal pyramidal neurons in vitro. PhTX-343 (2 microM) did not significantly change synaptic transmission mediated by AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid)/kainate receptors in the CA1 region of hippocampus. However, PhTX-343 significantly suppressed both the synaptic N-methyl-D-aspartate receptor-induced current (NMDA) obtained in the presence of CNQX(6-cyano-7-nitroquinoxaline-2,3-dione)/picrotoxin (10 microM) and the directly evoked NMDA receptor-induced current to pressure ejection of NMDA in the presence of tetrodotoxin (0.5 microM). A short transient facilitation of both types of NMDA response was seen immediately after the beginning of PhTX-343 application. Our results suggest that at high concentration (2 microM) PhTX-343 inhibits the NMDA-gated current, while the early facilitation occurred during an initial low concentration of the compound. Both facilitative and depressive actions of PhTX-343 are localized at the postsynaptic membrane.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1992

The maintenance of hippocampal long-term potentiation is paralleled by a dopamine-dependent increase in glycoprotein fucosylation.

Induction of long-term potentiation (LTP) in hippocampal slices of rats caused an increase in both protein synthesis and glycoprotein fucosylation by 38 and 34%, respectively. The enhanced incorporation of [3H]fucose into glycoproteins observed 1 h after tetanization was abolished in the presence of the dopamine D1 receptor antagonist SCH23390 during stimulation whereas the LTP-induced increase of protein synthesis was not influenced by this drug. The enhanced insertion of [3H]fucose into hippocampal glycoproteins 1 h after tetanization was paralleled by an increase in the activity of the fucose metabolizing enzyme, fucokinase. In contrast no changes in protein and glycoprotein synthesis were detectable 5 h after tetanization of the slices. The results provide evidence that in addition to an enhanced protein synthesis a dopamine (D1) mediated increase in glycoprotein fucosylation is necessary for the maintenance of the late stage of LTP.

Animals↗

PubMed1992

Philanthotoxin-343 blocks long-term potentiation in rat hippocampus.

The effects of extracellularly-applied synthetic philanthotoxin-343 (PhTX-343) on transmission and long-term potentiation (LTP) at Schaffer-collateral/commissural-CA1 synapses were investigated. PhTX-343 was ineffective in antagonizing CA1 field-EPSPs mediated by AMPA/kainate receptors. However, when a micromolar concentration of the toxin was present during tetanization, the induction of LTP was suppressed. In contrast, when PhTX-343 was applied either immediately after or long after tetanization no effect on LTP could be found. It appears that the synaptic, non-NMDA receptors of the CA1-region are insensitive to PhTX-343. Suppression of LTP induction could result from antagonism of postsynaptic NMDA receptors, but the results do not rule out other possibilities such as presynaptic block.

Animals↗

PubMed1991

The effect of dopaminergic D1 receptor blockade during tetanization on the expression of long-term potentiation in the rat CA1 region in vitro.

The effect of dopaminergic D1 receptor blockade on the expression of long-term potentiation (LTP) was investigated in the rat hippocampal CA1 region in vitro by extracellular recordings (by measuring the population spike amplitude and the field EPSP). The presence of the very selective D1 receptor blocker SCH 23390 at a concentration of 0.1 microM during tetanization with 3 trains of 100 impulses (100 Hz) resulted in a prevention of late LTP stages (greater than 1-2 h). When SCH 23390 was added to the bath medium immediately after tetanization, an influence on established LTP could not be observed during the first 3 h investigated.

Animals↗

PubMed1991

Differential effects of protein kinase inhibitors on pre-established long-term potentiation in rat hippocampal neurons in vitro.

The possibility that a permanent protein kinase C (PKC) activity is necessary for the maintenance of long-term potentiation (LTP) was investigated in rat hippocampal slices. The action of the potent kinase inhibitors K-252a, K-252b and staurosporine on LTP of orthodromic population excitatory postsynaptic potentials (EPSPs) recorded from CA1 pyramidal cells was tested both during tetanization and after establishment of LTP. Confirming earlier studies, all inhibitors applied during tetanization at a concentration of 50 nM eliminate late LTP. Only staurosporine, but not K-252a or K-252b, blocked already established late LTP (i.e. late application). Normal synaptic transmission was influenced only weakly by staurosporine. Considering that all inhibitors have similar potencies against PKC and were all effective if applied during tetanization these data suggest that the late maintenance of LTP depends on a staurosporine/H7-sensitive process (or kinase) rather than permanent activation of PKC.

Alkaloids↗

PubMed1991

L-2-amino-3-phosphonopropionate blocks late synaptic long-term potentiation.

The possible involvement of the metabotropic glutamate receptor in mechanisms of hippocampal long-term potentiation was investigated with the new antagonist 2-amino-3-phosphonopropionate (AP3). The action of D-AP3, D,L-AP3 and of the more selective L-isomer was tested on CA1 pyramidal cells in-vitro. If 100-300 microM of L- or D,L-AP3 was present during tetanization, post-tetanic and early long-term potentiation developed almost normally. However, starting from 100 min, LTP of the field-EPSP was eliminated in an irreversible manner. In contrast to the L-isomer, D-AP3 did not influence the course of LTP. These data suggest that the activation of the metabotropic glutamate receptor is necessary for subsequent mechanisms enabling the late maintenance of LTP.

Alanine↗