Metabotropic glutamate receptor enhancement of spontaneous IPSCs in neocortical interneurons

Academic Article


  • Using neocortical layer I neurons as a model for GABAergic interneurons, we have studied γ-aminobutyric acid-A (GABA(A)) receptor-mediated spontaneous inhibitory postsynaptic currents (IPSCs) and modulation by metabotropic glutamate receptors (mGluRs). In the presence of 0.5 μM tetrodotoxin (TTX) and ionotropic glutamate receptor antagonists and under symmetrical Cl- conditions, the mean amplitude of miniature IPSCs (mIPSCs) was ~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 ~0.6 ms. The decay was double exponential. The fast component had a time constant of ~4 ms and comprised ~40% of the total amplitude. The slow component had a time constant of ~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 μM) or the group I mGluR selective agonist quisqualic acid (Quis: 0.5-1 μM). Under identical conditions, mIPSCs were not affected. The kinetics of sIPSCs and mIPSCs were not altered by ACPD or Quis. Quis (1 μM) induced an inward current of ~70 pA at a holding potential of -70 mV, whereas ACPD (40-200 μM) 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 GABA(A) receptor-mediated inhibitory synaptic inputs. Activation of mGluRs, possibly mGluR1 and/or mGluR5, causes an enhancement of inhibitory synaptic transmission by directly depolarizing cortical GABAergic interneurons through the opening of nonselective cat-ion channels.
  • Authors

    Published In

    Digital Object Identifier (doi)

    Pubmed Id

  • 21114344
  • Author List

  • Zhou FUM; Hablitz JJ
  • Start Page

  • 2287
  • End Page

  • 2295
  • Volume

  • 78
  • Issue

  • 5