GABA_A receptor inhibition does not affect mGluR-dependent LTD at hippocampal Schaffer collateral-CA1 synapses

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 (GABA_AR) inhibition on mGluR-dependent long-term depression (LTD). Without GABA_AR blockade, mGluR-dependent LTD was induced pharmacologically by the group I mGluR agonist (RS)-3,5-dihydroxyphenylglycine (DHPG, 100 μM, 10 min) as well as electrically by paired-pulse low-frequency stimulation (PP-LFS, 900 paired pulses at 1 Hz) resulting in a stable depression of the field response lasting at least 80 min after LTD induction. The GABA_AR antagonist gabazine (5 μM) itself caused an increase of field responses suggesting an endogenous GABA release inhibiting CA1 field potentials. However, when either DHPG or PP-LFS was applied during GABA_AR inhibition, the field responses were significantly reduced. Moreover, normalizing these responses to experiments without GABA_AR blockade, there was no significant effect of gabazine on both DHPG- and PP-LFS-induced LTD. Thus, our results show that mGluR-dependent LTD at Schaffer collateral-CA1 synapses is unaffected by GABA_AR mediated synaptic transmission.