Membrane potential and intracellular Ca2+ oscillations activated by mGluRs in hippocampal stratum oriens/alveus...

Metabotropic glutamate receptors (mGluRs) are expressed heterogeneously in hippocampal interneurons, and their signal transduction cascades remain largely unclear. We characterized an oscillatory response activated by the mGluR agonist 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) in hippocampal interneurons of stratum oriens-alveus (OA) with simultaneous whole cell current-clamp recordings and intracellular Ca2+ imaging with confocal microscopy. 1S,3R-ACPD induced oscillatory membrane depolarizations and rises in intracellular Ca2+ that persisted in tetrodotoxin and were blocked by the antagonist of group I and II mGluRs (S)-alpha-methyl-4-carboxyphenylglycine. Membrane depolarizations and intracellular Ca2+ rises were blocked by extracellular Cd2+ and in Ca2+-free medium. mGluR responses therefore required Ca2+ influx via voltage-gated Ca2+ channels. 1S, 3R-ACPD responses were also antagonized by depleting intracellular stores with thapsigargin and ryanodine, indicating that Ca2+ release from intracellular stores was also necessary. These data suggest that oscillatory responses generated by group I/II mGluRs involve a coupling of Ca2+ entry through voltage-gated Ca2+ channels and Ca2+ release from internal stores. In contrast, 1S,3R-ACPD evoked only smaller depolarizations and intracellular Ca2+ rises, with no oscillations, in other hippocampal interneurons located in or near stratum lacunosum-moleculare. Thus mGluR-mediated oscillatory responses are specifically expressed in certain interneuron subtypes. This heterogeneous expression of glutamate and Ca2+ signaling pathways in specific interneurons may be relevant to their selective vulnerability to excitotoxicity.