Biomedical subjects

T Behnisch

Publications and source records attributed to T Behnisch.

24 records · Page 2Linked to original sources

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↗

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↗

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↗

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↗

PubMedDate not supplied

A specific role for group I mGluRs in hippocampal LTP and hippocampus-dependent spatial learning.

Metabotropic glutamate receptors (mGluRs) have been implicated in long-term potentiation and in learning and memory formation. In this study, we tested the effects of group I mGluR inhibition on synaptic plasticity and learning of rats at different levels of organization (1) in the hippocampal slice preparation; (2) in freely moving animals implanted with chronic hippocampal electrodes; and (3) in different spatial learning paradigms. To allow a direct comparison of the effects obtained the same doses were used in all paradigms. Bath-application of the selective group I mGluR antagonist (S)4-carboxyphenylglycine (4-CPG) impaired a decremental long-term potentiation (LTP) induced by a weak tetanization paradigm, but failed to affect a robust LTP generated by strong tetanization. In contrast, 4-CPG impaired a robust LTP in freely moving animals if applied 30 min before tetanization. The same dose of 4-CPG only impeded spatial learning mildly in the eight-arm radial maze and had no effect on a simple configuration of the Y-maze spatial alternation task. In the more difficult configuration of this task, however, 4-CPG caused complete amnesia. The lack of state-dependent 4-CPG actions and the absence of any 4-CPG effects in the open-field test classify the obtained retention deficit as a selective impairment of memory storage. Our results indicate a specific role of group I mGluRs in certain types of synaptic plasticity and of spatial learning.

Animals↗