PubMed Health⌕ Search

Biomedical subjects

K G Reymann

Publications and source records attributed to K G Reymann.

At least 55 records · Page 3Linked to original sources
PubMed1998

Subtype-specific involvement of metabotropic glutamate receptors in two forms of long-term potentiation in the dentate gyrus of freely moving rats.

In this study, the role of metabotropic glutamate receptors in N-methyl-D-aspartate receptor-dependent and voltage-gated calcium channel-dependent long-term potentiation in the dentate gyrus of freely moving rats was investigated. Antagonists for group 1 metabotropic glutamate receptors ((S)-4-carboxyphenylglycine), group 1/2 metabotropic glutamate receptors ((RS)-alpha-methyl-4-carboxyphenylglycine) and group 2 metabotropic glutamate receptors ((RS)-alpha-methylserine O-phosphate monophenylester) were used. The N-methyl-D-aspartate receptor antagonist, D(-)-2-amino-5-phosphonopentanoic acid, and the L-type voltage-gated calcium channel antagonist, methoxyverapamil were used to investigate the N-methyl-D-aspartate receptor and voltage-gated calcium channel contribution to the long-term potentiation recorded. Field excitatory postsynaptic potential slope and population spike amplitude were measured. Drugs were applied, prior to tetanus, via a cannula implanted into the lateral cerebral ventricle. 200 Hz tetanization produces a long-term potentiation which is inhibited by application of D(-)-2-amino-5-phosphonopentanoic acid and (RS)-alpha-methyl-4-carboxyphenylglycine. In this study, a dose-dependent inhibition of 200 Hz long-term potentiation expression was obtained with (S)-4-carboxyphenylglycine. Long-term potentiation induced by 400 Hz tetanization was not inhibited by D(-)-2-amino-5-phosphonopentanoic acid, although the amplitude of short-term potentiation was reduced. (RS)-alpha-methyl-4-carboxyphenylglycine and (S)-4-carboxyphenylglycine, both in the presence and absence of D(-)-2-amino-5-phosphonopentanoic acid, inhibited the development of 400 Hz long-term potentiation. (RS)-alpha-methylserine O-phosphate monophenylester had no significant effect on long-term potentiation induced by either 200 or 400 Hz tetanization. Application of methoxyverapamil significantly inhibited 400 Hz long-term potentiation, but had no effect on 200 Hz long-term potentiation. These data suggest that 400 Hz long-term potentiation, induced in the presence of D(-)-2-amino-5-phosphonopentanoic acid, requires activation of L-type calcium channels. Furthermore, these results strongly support a critical role for group 1 metabotropic glutamate receptors in both N-methyl-D-aspartate receptor- and voltage-gated calcium channel-dependent long-term potentiation.

2-Amino-5-phosphonovalerate↗
PubMed1997

Noise deconvolution based on the L1-metric and decomposition of discrete distributions of postsynaptic responses.

A statistical approach to analysis of amplitude fluctuations of postsynaptic responses is described. This includes (1) using a L1-metric in the space of distribution functions for minimisation with application of linear programming methods to decompose amplitude distributions into a convolution of Gaussian and discrete distributions; (2) deconvolution of the resulting discrete distribution with determination of the release probabilities and the quantal amplitude for cases with a small number (< 5) of discrete components. The methods were tested against simulated data over a range of sample sizes and signal-to-noise ratios which mimicked those observed in physiological experiments. In computer simulation experiments, comparisons were made with other methods of 'unconstrained' (generalized) and constrained reconstruction of discrete components from convolutions. The simulation results provided additional criteria for improving the solutions to overcome 'over-fitting phenomena' and to constrain the number of components with small probabilities. Application of the programme to recordings from hippocampal neurones demonstrated its usefulness for the analysis of amplitude distributions of postsynaptic responses.

Animals↗
PubMed1997

A post-tetanic time window for the reinforcement of long-term potentiation by appetitive and aversive stimuli.

Current theories on the encoding and storage of information in the brain commonly suppose that a short-term memory is converted into a lasting one; thus, it becomes consolidated over time. Within a finite period after training, such a short-term memory can be reinforced by behavioral and humoral stimuli. We have found that, long-term potentiation (LTP), a likely candidate for a memory-encoding mechanism at the cellular level, displays similar features. LTP in the dentate gyrus of freely moving rats was reinforced after its induction by appetitive and aversive stimuli. The efficacy of these stimuli terminates about 1 h after tetanization, which may reflect the time constants of the mechanisms underlying the consolidation that takes place. The reinforcement by appetitive and aversive stimulation was blocked by the beta-adrenergic antagonist propranolol, implicating norepinephrine in the underlying cellular processes.

Adrenergic beta-Antagonists↗
PubMed1997

Fast increases of AMPA receptor sensitivity following tetanus-induced potentiation in the CA1 region of the rat hippocampus.

Changes in sensitivity of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) subtype of glutamate receptors following the induction of long-term potentiation (LTP) were investigated in rat hippocampal slices. AMPA was ejected into the stratum radiatum of the hippocampal CA1 region by pressure ejection and the response recorded intracellularly. Responses to AMPA exhibited a fast increase (2-3 min) following LTP induction: the time course of this increase paralleled the potentiation of the excitatory postsynaptic current (EPSC). In cases where there was no increase in the slope of intracellularly recorded EPSC following tetanization, no increase of the AMPA responses was observed. These results suggest that increases in postsynaptic AMPA sensitivity can underlie short-term potentiation (STP) and thus, support a postsynaptic locus for both STP and LTP.

Animals↗
PubMed1997

Activation of phospholipases C and D by the novel metabotropic glutamate receptor agonist tADA.

In hippocampal slices taken from 8-day-old rats, trans-azetidine-2,4-dicarboxylic acid (tADA), a novel glutamatergic agonist acting preferentially at class I mGluR receptors, activates phosphoinositide and phosphatidylcholine hydrolysis with widely different potencies. Inositol phosphate formation was maximally increased at 10 microM tADA (EC50: 1.2 microM), while phospholipase D activation was observed at a tADA concentration of 1 mM. This is the first report of a tADA-induced phospholipase D activity.

Animals↗
PubMed1996

Histamine H3 receptor-mediated depression of synaptic transmission in the dentate gyrus of the rat in vitro.

1. The effects of histamine on excitatory synaptic transmission in the dentate gyrus region of rat hippocampal slices were examined using extracellular and whole-cell patch-clamp recording techniques. The GABAA receptor antagonist picrotoxin (50 microM) was present in the bath in all experiments. 2. Histamine (0.7-70 microM) reversibly depressed field excitatory postsynaptic potentials (fEPSPs) or excitatory postsynaptic currents (EPSCs) recorded intracellularly by up to 30%. The presynaptic fibre volley and EPSC reversal potential were unaffected by histamine, as were responses following pressure ejection of the glutamate receptor agonist S-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (S-AMPA) into the slice. 3. Histamine (7 microM) depressed equally the AMPA and N-methyl-D-aspartate (NMDA) components of the dual-component EPSC, recorded at -40 mV. 4. In addition to depressing synaptic transmission, histamine also reduced the magnitude of paired-pulse depression (PPD; 40 ms interpulse interval) of the medial perforant path EPSC. 5. Histamine depressed medial perforant path EPSCs more strongly than lateral perforant path EPSCs. Paired-pulse facilitation (PPF; 40 ms interpulse interval) in the lateral perforant path was enhanced by histamine. 6. The effects of histamine on synaptic transmission and PPD were mimicked by the selective H3 receptor agonist R-alpha-methylhistamine (0.1-10 microM) but not by the selective H2 receptor agonist dimaprit (10 microM). Similarly, the H3 receptor antagonist thioperamide (10 microM) blocked the effect of histamine whereas the H1 antagonist mepyramine (1 microM) and the H2 receptor antagonist cimetidine (50 microM) were ineffective. 7. Histamine actions on synaptic transmission and PPD were not occluded by application of the metabotropic glutamate agonist L-2-amino-4-phosphonobutyrate (AP4). 8. The results indicate that histamine depresses synaptic transmission in the dentate gyrus by binding to histamine H3 receptors located on perforant path terminals. The mechanism by which histamine depresses transmission is independent of that used by class III metabotropic glutamate receptors.

Animals↗
PubMed1996

Fast desensitizing kainate-gated current resolved in whole-cell experiments on isolated rat hippocampal neurons.

In whole-cell concentration-jump experiments on dissociated rat hippocampal neurons the existence of a fast desensitizing component of a kainate-gated current was demonstrated. More than 90% of all neurons tested possessed such a receptor. Electrophysiological and pharmacological data suggest an association of this fast kainate-gated current with that mediated through a combination of subunits forming a low-affinity "(RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolopropionic acid (AMPA)-preferring' receptor. Kinetic data suggest the existence of a compact spatial location of fast desensitizing "AMPA-preferring' receptors which are naturally expressed on the surface of the neurons. An AMPA-insensitive current component mediated through fast desensitizing high-affinity kainate receptors was not observed.

Animals↗
PubMed1996

Inhibition of TEA-induced LTP by aluminum.

Brief application of tetraethylammonium (TEA) to hippocampal slices causes long-term potentiation (TEA LTP) at synapses of CA1 pyramidal neurons characterized by a long-lasting increase of field excitatory postsynaptic potential (fEPSP) slope and population spike (PS) amplitude. Since this kind of potentiation requires the activation of voltage-dependent calcium channels, we examined the effect of the inorganic calcium channel blocker aluminum, which has been shown to impair tetanus-induced LTP (eLTP). We found that Al inhibited in a concentration-dependent manner both fEPSP slope and PS amplitude potentiation by TEA; 0.68 microgram/ml A1 attenuated TEA LTP, while a complete block of long-lasting potentiation was obtained for 2.7 micrograms/ml Al. Occlusion experiments revealed that both concentrations of Al allowed the induction of eLTP 60 min after TEA/Al exposure. However, longer application (15 min) of 2.7 micrograms/ml Al before the induction of TEA LTP prevented the subsequent induction of eLTP although no significant differences concerning the action on TEA LTP were observed. This indicates a general loss of neuronal plasticity which might be due to progressive neuronal cell damage. Since the effective concentration range of Al is directly comparable to the action of Al on eLTP, our data provide evidence for shared mechanisms of both potentiations. Although based on different induction mechanisms, Ca2+ is assumed to be a general intracellular trigger for both forms of LTP and thus it can be hypothesized that the neurotoxic action of Al is due to interference with Ca(2+)-dependent processes by inhibition of calcium conductances.

Aluminum↗
PubMed1996

Comparing the role of metabotropic glutamate receptors in long-term potentiation and in learning and memory.

1. Neuronal plasticity has been suggested to be the physical substrate for changes underlying the expression of memory. One model which has attracted wide attention as a possible candidate of such neuronal plasticity is long-term potentiation (LTP), mainly investigated in the hippocampus of rodents. Moreover, various processes with different time constants may underlie LTP, and these phases show striking correspondence to different phases of memory. 2. Pharmacological evidence strongly implicates that the neurotransmitter glutamate plays a major role in LTP. Although the involvement of ionotropic glutamate receptors has been proven, the role of the newly discovered metabotropic glutamate receptors is still uncertain. 3. Metabotropic glutamate receptors (mGluRs) comprise a whole family with currently eight members grouped into three classes according to their amino acid sequence identity and pharmacological profile. They are G-protein coupled, either positively linked to phospholipase C (class I) or negatively linked to adenylate cyclase (class II and III), and among other effects are known to induce phosphorylation of ionotropic glutamate receptors as well as modulate the excitability of neurons. Finally, they are heterogeneously distributed throughout the brain. 4. In hippocampal slice preparations, mGluRs have been shown to be involved in the induction of LTP in CA1 and dentate gyrus by some investigators, but others have failed to reproduce such experiments, leaving the question: what are the appropriate conditions for mGluR-mediated LTP? 5. In vivo, metabotropic receptor antagonists have been shown to block, and agonists to facilitate, induction and maintenance of LTP, mainly at perforant path/dentate granule cell synapses. As demonstrated in behavioral investigations, mGluRs apparently play an important part in hippocampus-dependent learning paradigms. As in LTP, antagonists block memory formation; in contrast to LTP, agonists also prevent memory formation. In memory recall metabotropic receptors seem to play no role. 6. Based on current information the authors develop models for a role of mGluRs in both LTP and memory formation. Activation of metabotropic receptors plays a particular modulatory role when high frequency stimulation is weak. Strong tetanization may bypass mGluRs by stimulating other systems leading to, at least phenomenologically, similar LTP, Behaviorally, mGluRs possibly set the signal to noise ratio of the hippocampal circuit.

Animals↗
PubMed1996

Physiological and pharmacological profile of trans-azetidine-2,4-dicarboxylic acid: metabotropic glutamate receptor agonism and effects on long-term potentiation.

In this study, we biochemically analysed the effects of the novel metabotropic glutamate receptor agonist trans-azetidine-2,4-dicarboxylic acid and examined its role in hippocampal long-term potentiation. In cell lines expressing metabotropic receptor 1 or 5 subtypes, the compound stimulated phosphoinositide hydrolysis with EC50 values of 189.4 +/- 6.4 and 32.2 +/- 8.3 microM, respectively. In hippocampal slices, trans-azetidine-2,4-dicarboxylic acid also increased phosphoinositide hydrolysis, yet failed to show any effect on forskolin-stimulated formation of cyclic AMP, even if 1 mM azetidine was applied. Since trans-azetidine-2,4-dicarboxylic acid (20 mM in 5 microliters) injected cerebroventricularly prolongs long-term potentiation induced by weak tetanization, a possible interaction with N-methyl-D-aspartate receptors was investigated using patch-clamp techniques. Neither facilitation of N-methyl-D-aspartate (500 microM) currents nor induction of non-specific currents was observed in the presence of 50 and 500 microM azetidine. Strong tetanus-induced long-term potentiation in the dentate gyrus of freely moving rats was not influenced by azetidine. In combination with the antagonist (R,S)-alpha-methyl-4-carboxyphenylglycine (200 mM in 5 microliters), however, the potentiation was attenuated and returned to baseline within 90 min. Blockade of N-methyl-D-aspartate receptors using 2-amino-5-phosphonopentanoate (20 mM in 5 microliters) prevented the potentiation in controls, but not in the azetidine group, where normal potentiation was observed for both the population spike amplitude and the excitatory postsynaptic potential. These data suggest that (i) trans-azetidine-2,4- dicarboxylic acid is an agonist at glutamate metabotropic receptors; (ii) a facilitation of induction and maintenance of long-term potentiation via N-methyl-D-aspartate receptors seems unlikely; and (iii) pharmacological activation of metabotropic receptors prior to tetanization appears to bypass the N-methyl-D-aspartate receptor dependence of the potentiation. In conclusion, a role for metabotropic glutamate receptors in both short-term and long-term potentiation is indicated by these data.

Animals↗
PubMed1996

Metabotropic glutamate receptor subtype agonists facilitate long-term potentiation within a distinct time window in the dentate gyrus in vivo.

Trans-azetidine-2,4-dicarboxylic acid (ADA) is a putative selective agonist of group 1 metabotropic glutamate receptors. It has been shown previously that application of ADA prior to a short-term potentiation-inducing high-frequency tetanus facilitates long-term potentiation in vivo. In order to examine the role of metabotropic glutamate receptors in this response, we studied the effect of ADA in the dentate gyrus of the rat when applied after high-frequency tetanus to the perforant path. A comparison was made with the effects of the metabotropic glutamate receptor group 1 agonist 3,5-dihydroxyphenylglycine. Drugs were applied via a cannula implanted in the lateral cerebral ventricle. Both population spike amplitude and field excitatory postsynaptic potential were measured. Weak tetanization produced a short-term potentiation of field excitatory postsynaptic potential and population spike which decayed to baseline values by 90 min, and was unaffected by vehicle injections. Application of ADA (20 mM/5 microliters) or 3,5-dihydroxyphenylglycine (4mM/5 microliters) 5 min after high-frequency tetanus facilitated short-term potentiation into a long-term potentiation which lasted over 24 h. (R,S)-alpha-Methyl-4-carboxyphenylglycine (200 mM/5 microliters), a metabotropic glutamate receptor antagonist, when applied prior to high-frequency tetanus and ADA or 3,5-dihydroxyphenylglycine, completely inhibited this effect. ADA applied 10,15,20 and 25 min after high-frequency tetanus also facilitated short-term potentiation into long-term potentiation, but the magnitude of long-term potentiation was smaller than than produced by ADA given 5 min after tetanus. Similar effects were seen with 3,5-dihydroxyphenylglycine applied 25 min after high-frequency tetanus. When (R,S)-alpha-methyl-4-carboxyphenylglycine was applied prior to high-frequency tetanus and ADA or 3,5-dihydroxyphenylglycine applied 30 min after high-frequency tetanus, or after short-term potentiation decay, elicited no facilitation of long-term potentiation. These results indicate that a distinct time window for the enhancement by ADA and 3,5-dihydroxyphenylglycine of short-term potentiation into long-term potentiation occurs in the dentate gyrus in vivo. This suggests that metabotropic glutamate receptor activation in long-term potentiation occurs within a finite period of time and may be mediated by group 1 metabotropic glutamate receptors. Furthermore, it suggests that metabotropic glutamate receptor modulation of N-methyl-D-aspartate receptors does not account for the role of metabotropic glutamate receptors in long-term potentiation.

Animals↗
PubMed1996

Blockade of metabotropic glutamate receptors protects hippocampal neurons from hypoxia-induced cell death in rat in vivo.

1. In this pilot study the authors examined the role of hippocampal metabotropic glutamate receptors (mGluRs) in hypoxia in vivo by determining frank neuronal cell death histologically 4 days after the first of three daily insults. 2. Adult male, Wistar rats, chronically prepared with cannulae, were intraventricularly injected with either saline or the metabotropic receptor antagonists L-AP3 (0.102 mg) or MCPG (0.208 mg) 30 min prior to hypoxic insult. 3. Histological analysis of hippocampal regions revealed attenuated neuronal cell loss in CA1 and CA3 in both L-AP3 and MCPG-treated animals. 4. These data suggest a participation of mGluRs in hypoxia-induced neuronal cell death.

Animals↗
PubMed1996

Metabotropic glutamate receptors in hippocampal long-term potentiation and learning and memory.

Glutamate receptors have been identified as important interfaces in learning and memory paradigms as well as in mechanisms of synaptic plasticity, such as long-term potentiation (LTP) and long-term depression (LTD), which are believed to be the underlying cellular basis of at least some forms of learning. Although investigations of G-protein-coupled receptors have a long history, those depending on ligand-binding of glutamate have only been discovered recently, and this is the reason why our knowledge about metabotropic glutamate receptors (mGluRs) is at present very limited. However, the development of relatively specific antagonists and agonists has enabled the analysis of the role of mGluRs in synaptic plasticity, mostly studied on the models of LTP and LTD. Among others, we have been able to demonstrate that activation of mGluRs is essential for induction and maintenance of long-lasting hippocampal LTP in vitro and in vivo. The work conducted by several groups, including ours, has now provided compelling evidence that mGluR activation is an important step in the cellular cascades leading to memory formation in vertebrates. This led us to assume, given that the hippocampus plays a prominent role in spatial rather than discrimination learning, that mGluRs may participate in the processing of spatial information via hippocampal mechanisms, and may thus be similarly important as N-methyl-D-aspartate receptors. This article surveys the literature dealing with mGluRs in hippocampal LTP and learning and memory. We will demonstrate that, although the understanding of cellular mechanisms of neuronal plasticity and of the pharmacology of learning and memory has advanced, the missing link to prove that LTP is a substrate for some form forms of learning still remains unsolved. Nevertheless, it appears reasonable to argue that mGluRs in LTP and learning may share some, but not all features, and it will be an interesting approach for further analysis to address the unresolved issues.

Animals↗
PubMed1995

1S,3R-ACPD dose dependently induces a slow onset potentiation in the dentate gyrus in vivo.

It has been demonstrated by others in vitro that application of 1S,3R-aminocyclopentane-2,3-dicarboxylic acid (ACPD) facilitates long-term potentiation and triggers a slow-onset potentiation in the hippocampus. This study examined the effect of ACPD in the dentate gyrus when applied in vivo. Weak tetanisation produced a short-term potentiation of field excitatory post-synaptic potential (EPSP) and population spike. A similar response was seen upon application of ACPD (40 microM in 5 microl vehicle) via the lateral cerebral ventricle 30 min prior to tetanus, whereas ACPD (80 microM/5 microl) facilitated short-term potentiation into long-term potentiation. (R,S)-alpha-Methyl-4-carboxyphenyl-glycine (MCPG 200 mM/5 microl), completely inhibited this effect. ACPD had no effect on baseline recordings at 40 and 80 microM/5 miccrol, however 4 mM/5 microl ACPD induced a slow-onset potentiation of field EPSP and population spike which was maintained for over 4 h. MCPG or D-2-amino-5-phosphonopentanoate (AP5 20 mM/5 microl) applied prior to ACPD completely inhibited this effect. These results suggest that previously reported in vitro effects of ACPD in the CA1 region, also occur in the dentate gyrus in vivo. Furthermore, they confirm that activation of mGlu receptors by ACPD in vivo facilitates long-term potentiation, and indicate that in the dentate gyrus, ACPD-induced slow-onset potentiation is NMDA receptor-dependent.

Action Potentials↗
PubMed1995

Class I metabotropic glutamate receptor agonists do not facilitate the induction of long-term potentiation in the dentate gyrus of the rat in vitro.

The possibility that activation of class I (phospholipase C-coupled) metabotropic glutamate receptors (mGluRs) can facilitate the induction of long-term potentiation (LTP) was investigated in the dentate gyrus of rat hippocampal slices. In the presence of picrotoxin, a weak tetanus led to a short-term potentiation (STP) lasting 10-15 min. Application of the class I mGluR agonists trans-azetidine-2,4-dicarboxylic acid (tADA, 100 microM) or 3,5-dihydroxyphenylglycine (DHPG, 100 microM) for 15 or 30 min before the weak tetanus did not affect baseline synaptic transmission or the magnitude of the subsequent potentiation. DHPG (70 microM) did, however, reduce accommodation of neuronal firing in response to depolarizing current injection. These results suggest that at the medial perforant path-granule cell synapse, class I mGluR activation by exogenous agonist application does not facilitate the induction of LTP.

Animals↗
PubMed1995

Open field behaviour in rats: role of metabotropic glutamate receptors.

Previous studies have shown that spatial memory retention is affected by the metabotropic glutamate receptor (mGluR) influencing agents (R,S)-alpha-methyl-4-carboxyphenylglycine (MCPG) and trans-azetidine-2,4-dicarboxylic acid (tADA). In the present investigation we examined whether the mGluR antagonist MCPG (20 mM and 200 mM/5 microliters, respectively) and the agonist tADA (20 mM/5 microliters) have other behavioural effects using the open field test on two successive days. Only minor effects of MCPG (decrease of crossings during the 1st min on day 1) and tADA (increase of rearings on both days) were found. These results suggest that memory influencing doses of MCPG and tADA have no or only little behavioural effects in the open field situation.

Animals↗
PubMed1995

Preferential block of desensitizing AMPA receptor in hippocampal neurons by gamma-D-glutamylaminomethylsulfonic acid.

The (RS)-alpha-Amino-3-hydroxy-5-methyl-4-isoxazolopropionic acid (AMPA)/kainate receptor-channel complex mediates fast components of excitatory synaptic currents in the central nervous system. Distinguishing between these components is a difficult pharmacological task. As was recently reported, gamma-D-glutamylaminomethylsulfonic acid (GAMS) may be a selective kainate receptor antagonist. We have tested this possibility in experiments which were carried out on acutely isolated rat hippocampal neurons. It appeared that 1 mM GAMS first blocked 83 +/- 1% of the fast desensitizing 128 microM AMPA-gated current, but only 38 +/- 6% of the non-desensitizing current component and reached, at higher GAMS concentrations, a plateau at about 50% of the control steady state current level. In contrast to the blocking action of GAMS on AMPA-gated currents, 4-fold higher concentrations of GAMS were needed to block currents elicited by 256 microM kainate application. It is suggested that several subunit compositions of the AMPA-gated receptor could coexist on a single hippocampal cell. Furthermore, GAMS has a certain preference for subunit assemblies which could mediate fast desensitizing and, a portion of, the non-desensitizing current component.

6-Cyano-7-nitroquinoxaline-2,3-dione↗