Activation of metabotropic glutamate receptors by repetitive stimulation in auditory cortex

To determine whether metabotropic glutamate receptors (mGluRs) contribute to the responses of neurons to repetitive stimulation in the rat auditory cortex in vitro, five stimulus pulses were delivered at 2-100 Hz which elicited five depolarizing synaptic responses, f-EPSPs: f-EPSPs(1-5). Stimulus pulses 2-5 delivered at low frequencies (2-10 Hz) elicited f-EPSPs(2-5) that were about 15% smaller than the response elicited by the first pulse (f-EPSP(1)). In the presence of the nonspecific mGluR agonist, ACPD, the amplitude of all f-EPSPs was 40% smaller than predrug responses. APV, CNQX, or bicuculline (antagonists of NMDA-, AMPA/kainate-, and GABA(A)-receptors, respectively) did not change this effect of ACPD. The mGluR antagonist, MCPG, had no effect on f-EPSPs but did reduce the effect of ACPD. High-frequency stimulation (50-100 Hz) elicited f-EPSPs that were smaller with each successive stimulus. In ACPD, f-EPSP(1) was 40% smaller than predrug, but f-EPSPs(3-5) were not changed compared to pre-ACPD f-EPSPs(3-5), indicating that ACPD occludes the effect of repetitive stimulation. MCPG increased f-EPSP(5) by 15%, indicating that a portion of the reduction of f-EPSPs during high-frequency stimulation is mediated by mGluRs. MCPG also partially blocked the effect of ACPD. In CNQX, ACPD only decreased EPSPs, but APV or bicuculline did not change the effect of ACPD. These results suggest that the successive reduction of f-EPSPs during a high-frequency train is partially a result of mGluR activation.