Biomedical subjects

K G Reymann

Publications and source records attributed to K G Reymann.

At least 73 records · Page 4Linked to original sources

PubMed1995

Metabotropic glutamate receptor agonists reduce paired-pulse depression in the dentate gyrus of the rat in vitro.

We have analyzed the effects of agonists acting at different classes of metabotropic glutamate receptors (mGluRs) on paired pulse depression (PPD) at the medial perforant path/granule cell synapse. Drugs were bath applied and paired pulses delivered at 3-min intervals during control and during drug application. Both 1S,3R-1-aminocyclopentane- 1,3-dicarboxylic acid (1S,3R-ACPD, 100 microM), which acts at class I (mGluR1, 5) and class II (mGluR2, 3) mGluRs and L-2-amino-4-phosphobutyric acid (L-AP4, 100 microM) which is specific for class III (mGluR4, 6-8) mGluRs, strongly reduced PPD with an interstimulus interval (ISI) of 40 ms (P < 0.001). The class I specific agonists trans-azetidine-2,4,dicarboxylic acid (t-ADA, 100 microM) and 3,5,dihydroxyphenylglycine (DHPG, 100 microM) did not affect PPD. The relatively specific class II agonists S-3-carboxy-4-hydroxyphenylglycine (3C4HPG) and 2S,3S,4S-alpha- carboxycyclopropyl-glycine (L-CCG-I) did reduce PPD, but only at very high concentrations (500 and 40 microM respectively) with respect to their EC50 values. These results suggest that two types of mGluRs control PPD at this synapse--a class III mGluR and a class II-like mGluR, which may not correspond to one of the currently cloned receptors.

Animals↗

PubMed1995

Thapsigargin blocks long-term potentiation induced by weak, but not strong tetanisation in rat hippocampal CA1 neurons.

To elucidate the role of calcium release from internal stores during different paradigms of tetanisation in long-term potentiation (LTP), we have investigated the effects of thapsigargin on the elevation of the excitatory postsynaptic field potential (fEPSP) and the population spike (PS) after tetanisation. We found no effect on the duration of fEPSP potentiation if thapsigargin was perfused before strong (triple) tetanisation. However, the potentiation was reduced significantly from control experiments if thapsigargin was applied before weak (single) tetanisation. Surprisingly, we did not find any reduction of PS potentiation, which could be due to changes in the recurrent inhibition. We conclude that the involvement of internal calcium release in the mechanisms of LTP induction will be reduced if multiple tetanisation is used.

Animals↗

PubMed1995

Antibodies to postsynaptic PKC substrate neurogranin prevent long-term potentiation in hippocampal CA1 neurons.

Both pre- and postsynaptic protein kinase C have been implicated in long-term potentiation. Neurogranin (also known as BICKs and RC3) is a neuronal postsynaptic protein kinase C substrate. In the present study we injected monoclonal IgGs that recognize the protein kinase C phosphorylation site in neurogranin and B-50 (GAP-43), and that have been shown to inhibit protein kinase C-mediated B-50 phosphorylation, through a whole-cell clamp pipette into CA1 pyramidal neurons in rat hippocampal slices. Injection of neurogranin IgGs, but not of control IgGs, prevented the induction of tetanus-induced long-term potentiation without affecting post-tetanic potentiation. Our results suggest that neurogranin is involved in mechanisms of activity-dependent synaptic plasticity.

Animals↗

PubMed1995

Aluminum impairs hippocampal long-term potentiation in rats in vitro and in vivo.

Although aluminum (Al) contributes to a variety of cognitive dysfunctions and mental diseases, the underlying mechanisms of Al interactions with the nervous system are still unknown. We have studied the action of Al on synaptic transmission and long-term potentiation (LTP) by performing electrophysiological recordings both in vivo, using freely moving animals, and in vitro, using hippocampal slices. In vivo recordings of the population spikes (PSs) of dentate gyrus granule cells in response to medial perforant path stimulation were performed on both acutely and chronically (Al each day for 5 days) intraventricularly injected animals. Acute Al-infusion (calculated brain concentrations of 0.27, 0.68, and 2.7 micrograms/ml) had no influence on baseline values. Al at 0.27 microgram/ml did not alter the induction and maintenance of LTP, but 0.68 and especially 2.7 micrograms/ml Al lead to a reduction in LTP, and the potentiation declined to baseline within 2 h. In chronic animals their neuronal responsiveness was reduced and in 30% of the rats the PS was completely lost. High-frequency tetanization failed to induce LTP. In slices, field potentials were evoked stimulating Schaffer collaterals and recording pyramidal cells of the CA1 region. Bath application of 0.68 microgram/ml Al increased the baseline amplitude of the PS slightly, whereas 2.7 micrograms/ml decreased the amplitude and concentrations > 5.4 micrograms/ml blocked the PS completely. Induction of LTP in the presence of 0.68 microgram/ml Al led to a smaller increase of the PS amplitude compared to controls, but the duration of LTP was not affected. In the presence of 2.7 micrograms/ml Al LTP was further reduced and declined to baseline levels within 60 min. Given that LTP is a form of synaptic plasticity underlying some forms of learning, our data suggest that both preparations are suitable models for investigating actions of Al-induced neurotoxicity.

Aluminum↗

PubMed1995

Attenuation of high-voltage-activated Ca2+ current run-down in rat hippocampal CA1 pyramidal cells by NaF.

Calcium currents in CA1 neurons from rat hippocampus were studied with the whole-cell, patch-clamp technique. Under control conditions high-voltage-activated (HVA) calcium currents activated from membrane potentials of -80 mV and -40 mV underwent "run-down". The rate of run-down of the current activated from -40 mV was significantly attenuated by inclusion of the G-protein activator NaF (1 mM) in the pipette and also irreversibly attenuated by brief batch application of NaF (10 mM). This effect was significantly reduced by inclusion of high (10 mM) ethyleneglycoltetraacetate (EGTA) concentrations in the pipette, suggesting an involvement of calcium-dependent processes. It is suggested that activation of guanine nucleotide-binding proteins by NaF leads to a long-lasting attenuation of HVA calcium current run-down in hippocampal CA1 cells.

Animals↗

PubMed1995

Histaminergic modulation of synaptic plasticity in area CA1 of rat hippocampal slices.

The effects of histamine on baseline synaptic transmission and long-term potentiation (LTP) were investigated in the CA1 region of rat hippocampal slices. Bath applied histamine reversibly and dose-dependently increased the amplitude of extracellularly recorded population spikes in the concentration range 0.1-100 microM by a maximum of 40%. At higher concentrations (10-100 microM) histamine also caused a small depression of field excitatory postsynaptic potentials (fEPSPs) of approx 10%. The effect of histamine on population spikes was found to be mediated through histamine H2 receptors. Histamine (10-100 microM) was found to produce a statistically significant LTP of fEPSPs when combined with a weak tetanus (0.25 sec, 50 Hz). Histamine H1 (mepyramine, 1 microM) and H2 (cimetidine, 50 microM) receptor antagonists did not block this enhanced potentiation. In addition, histamine (10-100 microM) enhanced the late portion of the response produced by pressure ejection of glutamate receptor agonist N-methyl-D-aspartate into the slice, as recorded extracellularly or intracellularly. This effect of histamine was only apparent when large NMDA responses were obtained, using a high pipette concentration of NMDA (1 mM). In the presence of histamine H1 and H2 antagonists, potassium channel blockers or blockade of inhibition, this enhancement could still be observed. We conclude that histamine facilitated the induction of LTP, most likely by acting directly at the NMDA receptor.

Animals↗

PubMed1995

Block of spatial learning by mGluR agonist tADA in rats.

As demonstrated recently, mGluRs are involved in some forms of learning. We thus investigated the effect of tADA (trans-azetidine-2,4-dicarboxylic acid) applied intracerebroventricularly prior to learning a spatial alternation paradigm. Compared to controls, tADA treated animals were amnesic when tested for retention 24 hr after training. Effects of state-dependency were excluded. These data and our earlier work indicate that both mGluR agonists and antagonists can have memory-disrupting effects.

Animals↗

PubMed1995

Regional and developmental profile of modulation of hippocampal synaptic transmission and LTP by AP4-sensitive mGluRs in vivo.

L-AP4 is an agonist at the presynaptic metabotropic receptor subtypes mGluR4, mGluR6 and mGluR7. In vitro, L-AP4 has been shown to reduce glutamate release and thereby suppress hippocampal excitatory transmission. Little data is available with regard to the actions of this compound in vivo. This study examined the effects of L-AP4 injected i.c.v. in the hippocampus of freely-moving rats on synaptic transmission and long-term potentiation (LTP). Two age groups were employed: 8-week-old and 12-week-old. Administration of L-AP4, 80 mM/5 microliters, reduced evoked baseline responses in the dentate gyrus (DG) and CA1 of 8-week-old rats when compared with controls. This effect was blocked by MCPG. L-AP4, 40 mM/5 microliters, also reduced baseline in DG but not CA1. L-AP4 (20, 40 or 80 mM/5 microliters) had no effect on baseline in either DG or CA1 of 12-week-old animals. However, injection of L-AP4 (80 mM/5 microliters) significantly reduced the amplitude of LTP induced by tetanization in CA1 and DG. This effect was blocked by MCPG (200 mM/5 microliters). LTP reduction, tested in 12-week-old animals, also occurred with an L-AP4 concentration of 40 mM/5 microliters in CA1 but not in DG. These data indicate that L-AP4 inhibits LTP in vivo with a variation in sensitivity to the drug occurring between regions. It is suggested that the response in CA1 is produced by mGluR7, and in DG by presynaptic mGluR4 present on perforant path neurons. These results offer in vivo physiological evidence for a variation in functional response and in developmental regulation of these subtypes, dependent on the region of the hippocampus where they are located.

Aminobutyrates↗

PubMed1995

1S,3R-ACPD dose-dependently induces a slow-onset potentiation in the rat hippocampal CA1 region in vivo.

It has been reported that application of 1S,3R-1-aminocyclopentane 1,3-dicarboxylic acid (ACPD) in vitro triggers a slow-onset potentiation in the hippocampal CA1 region. This study examined the effect of ACPD in the CA1 of freely moving rats. No effect on fEPSP baseline recordings occurred at 40 and 400 microM/5 microliters, however at 4 mM/5 microliters ACPD induced a slow-onset potentiation. MCPG (200 mM/5 microliters) completely inhibited this ACPD effect. These results indicate that slow-onset potentiation in the CA1 region, also occurs in vivo.

Animals↗

PubMed1995

Metabotropic glutamate receptor agonist trans-azetidine-2,4-dicarboxylic acid facilitates maintenance of LTP in the dentate gyrus in vivo.

We examined the role of metabotropic glutamate receptors by studying the effect of intracerebroventricular infusion of the putative mGluR agonist trans-azetidine-2,4-dicarboxylic acid (tADA) on long-term potentiation (LTP) in the dentate gyrus of freely moving rats. Weak tetanization caused a decremental potentiation which returned to baseline levels within 2 hr. Injections of tADA (20 mM/5 microliters) 30 min prior to weak tetanization prolonged LTP of the field EPSP for at least 24 hr.

Animals↗

PubMed1995

Metabotropic glutamate receptors are involved in TEA-induced long-term potentiation in area CA1 of the hippocampus.

A brief application of the K+ channel blocker tetraethylammonium induces a long-lasting potentiation in the CA1 region of hippocampal slices (TEA LTP). We report here that metabotropic glutamate receptors (mGluRs) contribute to this kind of synaptic enhancement, since the mGluR antagonist (+)-alpha-methyl-4-carboxyphenylglycine ((+) MCPG) inhibits TEA LTP with a concentration-dependent component.

Animals↗

PubMed1995

Drinking after water deprivation prolongs "unsaturated" LTP in the dentate gyrus of rats.

The role of different behavioral states was tested with respect to induction and duration of long-term potentiation (LTP), using strong or weak tetanic stimuli of the perforant path input to the dentate gyrus of freely moving male Wistar rats. Recording and stimulating electrodes were chronically implanted into the granule cell layer of dentate gyrus and the perforant path, respectively. The effect of tetanic stimulation during three different behavioral states was compared: (a) highly motivated drinking (HMD): Animals (water deprived before experiment 23 h per day on four consecutive days) were tetanized during drinking; (b) high motivation (HM): Animals were treated as the HMD group but received water 1 h after tetanization; and (c) nondeprived controls (NDC). A strong tetanization (10 bursts, 200 Hz) produced a "saturated" LTP for more than 24 h, which was not affected by the behavioral state. LTP induced by weak tetanization (3 bursts, 200 Hz), which usually declines to baseline after at most 7 h, was clearly prolonged by HMD (persisting for at least 24 h), but facilitated to a lesser extent by HM. We suggest that a psychological component that arises during drinking after water deprivation triggers mechanisms resulting in an overt strengthening of an "unsaturated" LTP after weak tetanization, but without having any effect on a "saturated" LTP induced by strong tetanization.

Animals↗

PubMed1995

Asymptotic hippocampal long-term potentiation in rats does not preclude additional potentiation at later phases.

Hippocampal long-term potentiation may serve as an elementary process underlying certain forms of learning and memory in vertebrates. As is the case with behavioural memory, hippocampal long-term potentiation in the CA1 region and in the dentate gyrus exhibits distinct phases. These comprise a short-term early potentiation which lasts one to three hours and is independent of protein synthesis and is characterized in general by the activation of N-methyl-D-aspartate receptors and protein kinases; and a later, longer lasting phase, which can be separated by inhibitors of protein synthesis. Here, we report that the prior induction of long-term potentiation, both in the dentate gyrus in vivo and in the CA1-region in vitro, precludes further long-term but not short-term potentiation by means of a newly delivered conditioning stimulus to a subset of the same activated synapse population during the early stage (approximately 1-3 hours post tetanus). In contrast, a subsequent, long-lasting potentiation can be induced after the establishment of the late phase of potentiation (> 4 h). Thus, the system preserves the capacity for short-term potentiation immediately after potentiation, but the capacity for the induction of longer lasting plastic changes is recovered only after about four hours. Our results demonstrate that, once long-term potentiation has been established, hippocampal neurons do not lose their capacity for functional plasticity during certain phases of the maintenance of long-term potentiation.

Animals↗

PubMed1995

Metabotropic glutamate receptor subtypes differentially influence neuronal recovery from in vitro hypoxia/hypoglycemia in rat hippocampal slices.

Hippocampal slices were transiently exposed to an oxygen- and glucose-free environment which causes a pronounced drop of both ATP and creatine phosphate, an anoxic depolarization, and an incomplete recovery of synaptically evoked population spike in the CA1 region after 1 h (48.5 +/- 3.6% of baseline values). This recovery could be markedly enhanced by the application of N-methyl-D-aspartate receptor antagonists. To examine the influence of metabotropic glutamate receptors on neuronal recovery from hypoxia/hypoglycemia, we applied various antagonists and agonists of the metabotropic glutamate receptors to the bath during the interval from 20 min before to 10 after hypoxia/hypoglycemia. The metabotropic glutamate receptor antagonists (+)-alpha-methyl-4-carboxyphenylglycine and L-2-3- amino-phosphonopropionic acid were both able to enhance the population spike recovery significantly. However, the mixed metabotropic glutamate receptor agonist 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid also exhibited a protective effect on population spike recovery, leaving the anoxic depolarization and N-methyl-D-aspartate responses during the hypoxia/hypoglycemia untouched. With the help of more subtype-specific agonists, we found that an activation of phospholipase C coupled (class 1) metabotropic glutamate receptors prior to hypoxia/hypoglycemia may be responsible for the protective effect seen with 1S, 3R-1-aminocyclopentane-1,3-dicarboxylic acid, because the specific class 1 metabotropic glutamate receptor agonist trans-azetidine-2,4-dicarboxylic acid appeared to be highly protective, but only if it was applied 20 min before the hypoxia/hypoglycemia. An activation of class 2 metabotropic glutamate receptors by (2S,1'R,2'R,3'R)-2-(2,3-dicarboxycyclopropyl)glycine, which inhibits adenylyl cyclase activity, led to a marked deterioration of the population spike recovery and even to a total prevention of the protective effect of the N-methyl-D-aspartate agonist D-2-amino-5-phosphonopentanoic acid. Our data suggest that prior activation of class 1 metabotropic glutamate receptors is beneficial, while their activation during hypoxia/hypoglycemia is detrimental. Furthermore, the activation of class 2 metabotropic glutamate receptors decreases the recovery from hypoxia/hypoglycemia.

Adenosine Triphosphate↗

PubMed1995

Inhibition of long-term potentiation in the dentate gyrus of freely moving rats by the metabotropic glutamate receptor antagonist MCPG.

Metabotropic glutamate receptors (mGluRs) are critically involved in the maintenance of long-term potentiation (LTP) (Reymann and Matthies, 1989; Behnisch et al., 1991; Izumi et al., 1991; Bashir et al., 1993). In order to assess further the physiological role of MGluRs in LTP, we injected freely moving rats with the recently available, competitive mGluR antagonist (R,S)-alpha-methyl-4-carboxyphenylglycine (MCPG) intraventricularly and recorded extracellularly the population spike (PS) as well as the field excitatory postsynaptic potential (fEPSP) of the granule cells of the dentate gyrus in response to stimulation of fibers of the perforant path. MCPG was administered in two concentrations (A = 20 mM/5 microliters; B = 200 mM/5 microliters) either 30 min prior to or 5 min after LTP induction. Sodium chloride infusion served as a control. Normal synaptic transmission was not altered by MCPG. However, the mGluR antagonist inhibited LTP in a concentration-dependent manner. Concentration A did not influence the potentiation shortly after the tetanus. In the PS, short-term potentiation (STP), which is decremental in its time course, occurred normally, but in contrast to controls the potentiation declined back to baseline values after 2-3 hr. This dose also reduced the posttetanic increase in the slope function of the fEPSP, and led to a time course of potentiation similar to that for the PS. Concentration B completely abolished the tetanus-induced potentiation. This block was similar to that obtained for the NMDA antagonist 2-amino-5-phosphonopentanoate (AP5). Both MCPG concentrations had no influence on the time course of preestablished LTP. These effects seem to be due to the action of the (+)-isomer of MCPG, since intracerebroventricular application of the (-)-isomer was without effect on the duration and magnitude of LTP. In addition, we were interested in the mGluR subtypes involved in the blocking mechanism of MCPG. 1S,3R-aminocyclopentane-1,3-dicarboxic acid (ACPD)-activated PPI hydrolysis in hippocampal slices was competitively inhibited by MCPG at a concentration of 1 mM or higher. In contrast, this concentration of MCPG did not affect the reduction of forskolin-stimulated cAMP formation by ACPD. These results corroborate recent findings that mGluRs are required for the induction of LTP in CA1 and CA3 in vitro (Bashir et al., 1993; Sergueeva et al., 1993) and in vivo (Riedel and Reymann, 1993). The process of STP is found to be independent of mGluR activation.(ABSTRACT TRUNCATED AT 400 WORDS)

2-Amino-5-phosphonovalerate↗

PubMed1994

Abscisic acid potentiates NMDA-gated currents in hippocampal neurones.

NMDA receptor functioning underlies the basic mechanism of synaptic plasticity of the central nervous system. The NMDA receptor is a subject for modulation by certain substances: facilitation of this receptor is thought to be crucial for the induction of plasticity phenomena. In the present investigation evidence for a potentiation of the NMDA-receptor by trans,trans-abscisic acid (postulated endogenous substance) is provided. Pre-exposure to trans,trans-abscisic acid induced a marked increase mainly of the fast component of NMDA-gated currents in isolated rat hippocampal neurones. The potentiating effect depended on an extracellular trans,trans-abscisic acid concentration with an EC50 value about 440 microM, Hill coefficient 2. Such a facilitatory effect developed rather slowly with a time constant of about 3 s. The results obtained imply the existence of a novel mechanism of NMDA receptor potentiation. The data presented indicate a possible neurophysiological significance of abscisin.

Abscisic Acid↗

PubMed1994

Computer-assisted shock-reinforced Y-maze training: a method for studying spatial alternation behaviour.

Y-mazes are widely used for discrimination learning and spatial alternation tasks. We present here a computer-assisted Y-maze model for spatial alternation learning via footshock reinforcement. No intramaze cues are provided and handling between trials is no longer required. Pretraining application of scopolamine (1 mg kg-1) and D-AP5 (2-amino-5-phosphonopentanoate; 0.016 mg) clearly impairs acquisition and retention (tested 24 h after acquisition) of spatial alternation. These effects are not due to state-dependent changes caused by drug treatment. Similar results were reported by others in food-motivated spatial alternation tasks as well as spontaneous alternation paradigms. The data support our model as a useful tool for studying spatial alternation in the Y-maze.

2-Amino-5-phosphonovalerate↗

PubMed1994

Metabotropic glutamate receptor agonist DCG-IV as NMDA receptor agonist in immature rat hippocampal neurons.

The electrophysiological action of (2S,1'R;2'R,3'R)-2-(2,3-dicarboxycyclopropyl)glycine (DCG-IV) on the NMDA receptor was investigated with the help of concentration-jump experiments on freshly dissociated hippocampal CA1 and CA3 neurons of rats. Inward currents elicited by a pulse of DCG-IV were insensitive to 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and could be blocked by D-(-)-2-amino-5-phosphonopentanoic acid (D-AP5) and magnesium and enhanced by glycine. The substance displayed cross-desensitization with NMDA but not with kainate or (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA). Dose-response curves showed that DCG-IV was weaker than NMDA but more potent than glutamate in eliciting agonist-gated currents. From these data we conclude that DCG-IV has to be used with caution as a tool for the investigation of metabotropic glutamate receptors.

2-Amino-5-phosphonovalerate↗