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K G Reymann

Publications and source records attributed to K G Reymann.

At least 19 recordsLinked to original sources
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↗
PubMed1991

Blockade of metabotropic glutamate receptors protects rat CA1 neurons from hypoxic injury.

The possible involvement of the metabotropic glutamate receptor in mechanisms of posthypoxic neuronal damage was investigated in an in-vitro model of mild hypoxia with the stereoselective antagonist L-2-amino-3-phosphonopropionate (L-AP3). When 300 microM L-AP3 was present during hypoxia the evoked field potentials (population EPSP and population spike in the CA1 region of the hippocampus) recovered to about 80-100% of baseline values. The recovery without drug treatment reached only 40-75%. The NMDA antagonist D,L-2-amino-5-phosphonovalerate (100 microM) was equally effective as L-AP3, whereas the less effective and less specific isomer D-AP3 (300 microM) did not show any protective effect. The results suggest that the activation of metabotropic glutamate receptors plays a role in hypoxic injury.

2-Amino-5-phosphonovalerate↗
PubMed1991

Enhanced sensitivity of "metabotropic" glutamate receptors after induction of long-term potentiation in rat hippocampus.

Stimulation of [3H]inositol monophosphate ([3H]InsP) formation by ibotenate or trans-1-aminocyclopentyl-1,3-dicarboxylic acid (t-ACPD) in rat hippocampal slices was enhanced after tetanic stimulation of the Schaffer collaterals projecting to the CA1 region (in vitro) or the perforant pathway projecting to the dentate gyrus (in freely moving animals). This effect was observed 5 h (but not 2 h) after long-term potentiation (LTP) induction and was abolished if tetanic stimulation was performed in the presence of specific antagonists of N-methyl-D-aspartate receptors. The delayed increase in excitatory amino acid-induced polyphosphoinositide (PPI) hydrolysis was accompanied by an enhanced responsiveness to norepinephrine, whereas the basal and carbamylcholine-stimulated [3H]InsP formation were unchanged. These results suggest that an increased activity of "metabotropic" glutamate receptors may contribute to the synaptic mechanisms enabling the late expression and or maintenance of LTP. Accordingly, LTP decayed more rapidly (within 5 h) in rats repeatedly injected with LiCl (60-120 mg/kg, i.p., for 10 days), a treatment that led to a reduced efficacy of ibotenate and norepinephrine in stimulating PPI hydrolysis in hippocampal slices.

Animals↗
PubMed1990

N-methyl-D-aspartate stimulates the release of dopamine from rat hippocampal slices.

Rat hippocampal slices were loaded with [14C]dopamine (DA) and superfused continuously with oxygenated Mg2(+)-free Krebs-Henseleit solution. A 5-min pulse of 1 mM N-methyl-D-aspartate (NMDA) temporarily enhanced the basal release of DA by 30%. This effect was blocked by 50 microM D,L-2-amino-5-phosphonovalerate, a selective NMDA receptor antagonist, as well as by 0.5 microM tetrodotoxin. These results suggest that NMDA receptors on hippocampal interneurons may modulate the DA release. A possible link between the NMDA-induced release of DA and mechanisms enabling the maintenance of synaptic long-term potentiation in the hippocampus is discussed.

2-Amino-5-phosphonovalerate↗
PubMed1989

Temporally distinct pre- and post-synaptic mechanisms maintain long-term potentiation.

Long-term potentiation (LTP) in the hippocampus is widely studied as the mechanisms involved in its induction and maintenance are believed to underlie fundamental properties of learning and memory in vertebrates. Most synapses that exhibit LTP use an excitatory amino-acid neurotransmitter that acts on two types of receptor, the N-methyl-D-aspartate (NMDA) and quisqualate receptors. The quisqualate receptor mediates the fast synaptic response evoked by low-frequency stimulation, whereas the NMDA receptor system is activated transiently by tetanic stimulation, leading to the induction of LTP. The events responsible for maintaining LTP once it is established are not known. We now demonstrate that the sensitivity of CA1 neurons in hippocampal slices to ionophoretically-applied quisqualate receptor ligands slowly increases following the induction of LTP. This provides direct evidence for a functional post-synaptic change and suggests that pre-synaptic mechanisms also contribute, but in a temporally distinct manner, to the maintenance of LTP.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1989

2-Amino-4-phosphonobutyrate selectively eliminates late phases of long-term potentiation in rat hippocampus.

The possible involvement of 2-amino-4-phosphonobutyrate (APB) recognition sites in mechanisms enabling the maintenance of long-term potentiation (LTP) was investigated in rat hippocampal slices. The action of D(-)- and L(+)-isomers of APB was tested on orthodromic EPSP and spike responses recorded extracellularly from CA1 pyramidal cells. If a moderate concentration (50 microM) of one or the other APB isomer was present during tetanization, posttetanic and early long-term potentiation developed nearly normally. However, from 2h onward LTP of both EPSP and spike potentiation was eliminated in an irreversible manner (8 h experiment). D-APB (L-isomer not tested) applied shortly after tetanization caused nearly the same delayed decline of LTP. No consistent effects of APB were seen in non-tetanized slices. Considering previous findings these data suggest that besides the obligatory NMDA receptor activation an APB-sensitive component expressed during and after tetanization is a necessary step for subsequent mechanisms enabling the late maintenance of LTP.

Action Potentials↗
PubMed1989

N-methyl-D-aspartate receptor activation is required for the induction of both early and late phases of long-term potentiation in rat hippocampal slices.

The possible involvement of N-methyl-D-aspartate (NMDA) receptors in mechanisms enabling the maintenance of long-term potentiation (LTP) was investigated in rat hippocampal slices. The action of the specific NMDA receptor antagonists (-)-2-amino-7-phosphonoheptanoic acid (D-APH) and 2-amino-5-phosphonovaleric acid (DL-APV) as well as of the inactive isomer L-APH was tested on orthodromic population excitatory postsynaptic potential (EPSP) and population spike (PS) responses recorded extracellularly from CA1 pyramidal cells. If the active D-isomer of APH (10 microM) or DL-APV (50 microM), but not if L-APH was present during tetanization, both EPSP and spike potentiation were markedly reduced or even blocked for the whole recording period (8 h after tetanization). It is concluded that the NMDA receptor component expressed during tetanization is a necessary step not only for initiation but also for subsequent mechanisms enabling late phases of synaptic LTP. Some remaining potentiation of the population spike may be related to a second, NMDA-independent mechanism.

2-Amino-5-phosphonovalerate↗
PubMed1989

4-beta-phorbol-12,13-dibutyrate enhances K+-stimulated dopamine release from hippocampal slices.

Slices of rat hippocampus were labelled with [14C]dopamine, superfused continuously with oxygenated Krebs-Henseleit solution and stimulated with a potassium pulse (48 mM K+, 5 min.). 4-beta-phorbol-12,13-dibutyrate (PDB), an activator of protein kinase C (PKC), enhanced the potassium-evoked overflow of 14C. This effect was blocked by prior application of polymyxin B, a relatively selective inhibitor of PKC. In contrast, the PKC-inactive 4-alpha-phorbol-12,13-didecanoate (PDD) had no influence on the evoked transmitter overflow. The results suggest that PKC may also be involved in the regulation of hippocampal DA release. A possible link between PKC activation and DA release to processes of synaptic long-term potentiation is discussed.

Animals↗
PubMed1988

Inhibitors of calmodulin and protein kinase C block different phases of hippocampal long-term potentiation.

The effects of a calmodulin (CaM) inhibitor, which does not influence Ca2+ fluxes (calmidazolium, RO-24571), and a new potent inhibitor of protein kinase C (K-252b) on long-term potentiation (LTP) were compared in hippocampal slices. Tetanic stimulation of the stratum radiatum during perfusion of calmidazolium (50 nM) failed to induce the characteristic post-tetanic and long-term increase in the magnitude of CA1-evoked responses. During perfusion with K-252b (50 nM) post-tetanic potentiation and initial LTP is expressed normally, but thereafter declines back to baseline with a 60 min delay. By themselves, the inhibitors had no significant effect on synaptic transmission in a non-tetanized control input. Our data are in line with current evidence from several laboratories that CaM- and protein kinase C (PKC)-dependent processes are involved in LTP and support the hypothesis that CaM mediates initiation and that PKC mediates mechanisms underlying the maintenance of LTP.

Action Potentials↗
PubMed1988

Anisomycin, an inhibitor of protein synthesis, blocks late phases of LTP phenomena in the hippocampal CA1 region in vitro.

Long-term potentiation (LTP) with its extremely long duration has been frequently regarded as an elementary mechanism of information storage in the nervous system or at least as a suitable model for the study of mechanisms underlying functional plasticity and processes of learning and memory formation. Considering the necessity of an increased protein synthesis for memory consolidation and for the maintenance of LTP in granular synapses in vivo it was of interest to determine whether the LTP of the CA1 region of the hippocampus depends on protein synthesis as well. For the solution of this question anisomycin (ANI), a reversible blocker of protein synthesis, was used at a concentration of 20 microM, which blocked the [3H]leucine incorporation in hippocampal slices by at least 85%. It has been shown that in the CA1 region in vitro the maintenance of LTP (i.e. a late phase greater than 5 h) depends on an ongoing protein synthesis. A 3-h treatment with ANI immediately following multiple tetanization resulted in gradually developing loss of field excitatory postsynaptic potential (EPSP) and population spike (PS) potentiation (15 +/- 19% increase of the PS instead of the 96 +/- 14% increase in non-treated control experiments at the 8th h after tetanization). Furthermore, a late PS potentiation (greater than 6 h) of a second non-tetanized pathway to CA1 pyramidal cells has been observed (increase by 64 +/- 18% at the 8th h) for the first time. This potentiation was ANI-sensitive as well and suggests that the maintenance of LTP is dependent on a postsynaptic mechanism.

Action Potentials↗
PubMed1988

Polymyxin B, an inhibitor of protein kinase C, prevents the maintenance of synaptic long-term potentiation in hippocampal CA1 neurons.

The involvement of protein kinase C (PKC)-mediated processes in mechanisms of long-term potentiation (LTP) was suggested by recent studies which have demonstrated a correlation between PKC activation and LTP. However, it was not possible to tell whether there is a causal relationship between the two events. Therefore, we have examined the induction and maintenance of LTP in rat hippocampal slices in the presence of a relatively selective PKC inhibitor, using extracellular electrophysiological techniques. Bath application of 0.1-100 microM polymyxin B did not influence the occurrence of post-tetanic and long-term potentiation usually seen in test responses 1 and 10 min after a 100-Hz/1 s tetanic stimulation of stratum radiatum fibers. However, 20 microM polymyxin B significantly depressed the increase in population spike amplitude and population excitatory postsynaptic potential (EPSP) slope from 30 to 120 min onwards, following repeated tetanization. Immediately after the drug application only weak and reversible effects were seen by the same parameters in test responses of a non-tetanized control input. A late (greater than 6 h) heterosynaptic potentiation of the population spike in the control input was blocked by polymyxin B treatment. Whereas the EPSP-LTP was fully blocked, some potentiation of the population spike still remained, suggesting the independence of PKC of the additional spike (E/S) potentiation for the first 6 h. These results provide direct evidence that the PKC activation is not essential for the initial phase of LTP, but is a necessary condition for a medium and a late, protein synthesis-dependent phase in this monosynaptic pathway, i.e. for the maintenance of synaptic LTP.

Action Potentials↗
PubMed1988

Phorbol ester-induced hippocampal long-term potentiation is counteracted by inhibitors of protein kinase C.

As was shown previously (Reymann et al. 1988), the protein kinase C (PKC)-inhibitor polymyxin B prevents the maintenance of electrically induced long-term potentiation (LTP) of synaptic transmission to CA1 neurons, indicating that posttranslational phosphorylation processes mediated by PKC are involved in mechanisms underlying this form of synaptic plasticity. To make sure that 1.) the polymyxin B actually acts against PKC activation and 2.) the long-lasting potentiation elicited by phorbol esters (Malenka et al. 1986) is mediated by PKC-activation, we have tested polymyxin B as well as the potent PKC-inhibitor K-252b during phorbol ester-induced LTP. 4-beta-phorbol-12,13-dibutyrate (PDBu) - a known activator of protein kinase C, induces a remarkable potentiation at concentrations as low as 0.5 microM. When 20 microM polymyxin B or 40 nM K-252b was administered to rat hippocampal slices prior to such a weak phorbol ester treatment, this potentiation did not develop with the exception of a small increase in the population spike in spite of polymyxin B-treatment (42% instead of 120% increase at 2 h after PDBu). In contrast, spike potentiation induced by high concentrations of PDBu (10 microM) could not be counteracted by 100 microM polymyxin B. It is concluded that at low concentrations the phorbol ester-induced potentiation is mainly mediated by a selective activation of protein kinase C and that the prevented maintenance of electrically induced LTP by polymyxin B is in fact due to inhibition of this kinase. The spike potentiation developed faster than that of the EPSP raising the possibility that PDBu activates two separate PKC-dependent processes.

Action Potentials↗