Metabotropic glutamate receptor enhancement of spontaneous IPSCs in neocortical interneurons

Metabotropic glutamate receptor enhancement of spontaneous IPSCs in neocortical interneurons. J. Neurophysiol. 78: 2287-2295, 1997. Using neocortical layer I neurons as a model for GABAergic interneurons, we have studied gamma-aminobutyric acid-A (GABAA) receptor-mediated spontaneous inhibitory postsynaptic currents (IPSCs) and modulation by metabotropic glutamate receptors (mGluRs). In the presence of 0.5 mu M tetrodotoxin (TTX) and ionotropic glutamate receptor antagonists and under symmetrical Cl- conditions, the mean amplitude of miniature IPSCs (mIPSCs) was approximately 50 pA at a holding potential of -70 mV with individual events ranging from 10 to 400 pA. Averaged mIPSCs had a 10-90% rise time of approximately 0.6 ms. The decay was double exponential. The fast component had a time constant of approximately 4 ms and comprised approximately 40% of the total amplitude. The slow component had a time constant of approximately 22 ms. The frequency of spontaneous IPSCs (sIPSCs), recorded in the absence of TTX, was increased by bath application of the mGluR agonist 1S,3R-1-aminocyclopentane-1, 3-dicarboxylic acid (ACPD; 10-100 mu M) or the group I mGluR selective agonist quisqualic acid (Quis; 0.5-1 mu M). Under identical conditions, mIPSCs were not affected. The kinetics of sIPSCs and mIPSCs were not altered by ACPD or Quis. Quis (1 mu M) induced an inward current of approximately 70 pA at a holding potential of -70 mV, whereas ACPD (40-200 mu M) induced a smaller inward current. This current was linear over the voltage range -70 to +30 mV and reversed polarity near 0 mV. In current-clamp recordings, both Quis and ACPD induced a depolarization and action potential firing in layer I and deeper layer interneurons. We conclude that neocortical layer I neurons receive GABAA receptor-mediated inhibitory synaptic inputs. Activation of mGluRs, possibly mGluR1 and/or mGluR5, causes an enhancement of inhibitory synaptic transmission by directly depolarizing corticalGABAergic interneurons through the opening of nonselective cation channels.