Hippocampal synaptic plasticity between Schaffer collaterals and CA1 pyramidal neurons can be induced by activation of N-methyl D-aspartate receptors (NMDARs) or of metabotropic glutamate receptors (mGluRs). Inhibitory GABAergic interneurons in this region abundantly terminate on pyramidal neurons and may thus influence synaptic plasticity. Although NMDAR-dependent synaptic plasticity is known to be influenced by inhibitory interneurons, little is known about the role of GABA on mGluR-dependent plasticity.

Here, we used field potential recordings of the Schaffer collateral-CA1 synapses in rat hippocampal slices in order to study the effect of GABA_A receptor inhibition on mGluR-dependent long-term depression (LTD). In control experiments, mGluR-dependent LTD was induced pharmacologically by the group I mGluR agonist DHPG (100 mM, 10 min) as well as electrically by paired-pulse low-frequency stimulation (PP-LFS, 900 paired pulses, 1 Hz, double stimulation strength) resulting in a stable depression of the field response lasting at least 80 minutes after LTD induction. The GABA_A receptor antagonist gabazine (5 mM) itself caused an increase of field responses suggesting an endogenous GABA release inhibiting CA1 field potentials. But both DHPG application and PP-LFS induced stable LTD, when gabazine was present during the whole experiment. However, there was surprisingly no significant effect on both DHPG- and PP-LFS-induced LTD under control conditions.

Thus our results show that mGluR-dependent LTD at Schaffer collateral-CA1 synapses is unaffected by GABAergic interneurons.