The effect of mGlu2/3 receptors on synaptic activities to different types of GABAergic interneurons in the anterior cingulate cortex

Abstract

Antagonists of the group II metabotropic glutamate (mGlu) 2/3 receptors have been shown to have a rapid antidepressant effect. GABAergic interneurons play a crucial role in major depressive disorder (MDD) and possibly mediate the rapid antidepressant effect. However, how mGlu2/3 receptors regulate synaptic activities to GABAergic interneurons is not fully understood. In the present work, we studied the effect of mGlu2/3 receptors on excitatory and inhibitory synaptic activities to somatostatin (SST)- and parvalbumin (PV)-expressing interneurons, two major types of GABAergic interneurons, in the anterior cingulate cortex (ACC) that is strongly indicated in MDD. We found that activation of mGlu2/3 receptors by (2S,2′R,3′R)-2-(2′,3′-dicarboxycyclopropyl) glycine (DCG-IV), an agonist of mGlu2/3 receptors, remarkably reduced the frequency, but not the amplitude, of spontaneous and miniature excitatory postsynaptic currents (sEPSCs and mEPSCs) and the amplitude of evoked EPSCs in both types. The reduction in the frequency of sEPSCs and the amplitude of evoked EPSCs was more pronounced in SST interneurons. DCG-IV, however, did not affect spontaneous and miniature inhibitory postsynaptic currents (sIPSCs and mIPSCs) and evoked IPSCs in both types. LY341495, an antagonist of mGlu2/3 receptors, enhanced the amplitude of evoked EPSCs without affecting sEPSCs and mEPSCs in both types. It also did not affect sIPSCs and evoked IPSCs except slightly increasing the frequency of mIPSCs in SST interneurons. Our results indicate that mGlu2/3 receptors primarily regulate excitatory synaptic activities to the two types of GABAergic interneurons in the ACC.