26th Annual Meeting of the Society for Neuroscience, November 16-21, 1996, Washington, D.C.

The involvement of metabotropic glutamate class I receptors in LTP depends on tetanisation strength

V. Wilsch, T. Behnisch*, T. Jager, D. Balschun, R. Pellicciari and K.G. Reymann


The eight subtypes of the metabotropic glutamate receptors (mGluRs) which are known so far can be pharmacologically divided in three classes. Beyond other functions mGluRs were found to play a role in synaptic plasticity. ACPD an mGluR class 1 and 2 agonist enhanced LTP whereas MCPG an unspecific mGluR class 1 and 2 antagonist led either to an inhibition of LTP or had no effect. To further resolve the role of class 1 mGluR in LTP, we employed MCPG and the specific class 1 antagonist 4-CPG and (RS)-1-Aminoindan-1,5-dicarboxylic acid (UPF 523) as well as the specific class 1 agonist DHPG in two different types of LTP.
Field excitatory postsynaptic potentials (fEPSPs) were recorded in the hippocampal CA1 area and a ´weak´ or a ´strong´ LTP were induced by two different tetanisation paradigms (tree trains of 100 Hz for 500 ms every 2 minutes or a single train of 100 Hz for 400 ms, pulsewidth 200 µs).
In the ´weak´ LTP, MCPG (400 µM) and 4-CPG (100 µM) led to clear-cut reduction of potentiation in comparison to controls. DHPG (15 µM) resulted in a decline of baseline values immediately after application which masked a facilitation of LTP induction. However, 50 min after tetanisation when this baseline depression had ceased the potentiation was significantly enhanced compared to controls. 4-CPG acted in a concentration dependent manner with an IC50 of 9.9±0.7 µM and a Hill coefficient of 1.03. UPF 523 had no effect which can be attributed to its supposed selectivity towards mGluR1 which seems to be limited to glial cells and CA1 interneurons. All drugs did not exert any influence on ´strong´ LTP. We conclude that activation of class 1 mGluR plays a role in a ´weak´ LTP but in the ´strong´ LTP other mechanisms compensate mGluR activation.

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