Modulatory effects of activation of metabotropic glutamate receptors on GABAergic circuits in the mouse cortex.

Metabotropic glutamate receptors (mGluRs) have a ubiquitous distribution in the central nervous system and often serve to regulate the release of neurotransmitters. We have previously shown that activation of both presynaptic and postsynaptic mGluRs can affect the gain of glutamatergic inputs in both thalamus and cortex. In the present study, we sought to determine the effect of mGluR activation on GABAergic inputs in cortex. Using whole cell recordings in a mouse slice preparation of either primary visual or auditory cortex (V1 or A1), we tested the effects on mGluRs by applying various agonists to the slice. Two pathways were tested in each area: the GABAergic inputs in layers 2/3 activated from layer 4 and the GABAergic inputs in layer 4 activated from adjacent layer 4. In both of these pathways, we found that activation of mGluRs significantly reduced the amplitude of the evoked inhibitory postsynaptic currents. Because the effects were not blocked by the addition of GDPβS to the recording electrode, and because mGluR agonists did not affect responses to photostimulation of GABA in a low-Ca(2+) and high-Mg(2+) bathing solution, we concluded this reduction was due to activation of presynaptic mGluRs. Furthermore, using specific mGluR agonists, we found that group II mGluRs, but not group I mGluRs, were involved in these modulatory effects. Because similar results were found in both pathways in V1 and A1, a possible cortical pattern for these effects is suggested.