Membrane potential and intracellular Ca2+ oscillations activated by mGluRsin hippocampal stratum oriens/alveus interneurons

Metabotropic glutamate receptors (mGluRs) are expressed heterogeneously in hippocampal interneurons, and their signal transduction cascades remain lar gely unclear. We characterized an oscillatory response activated by the mGl uR agonist 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) in hippocampal interneurons of stratum oriens-alveus (OA) with simultaneous wh ole cell current-clamp recordings and intracellular Ca2+ imaging with confo cal microscopy. 1S,3R-ACPD induced oscillatory membrane depolarizations and rises in intracellular Ca2+ that persisted in tetrodotoxin and were blocke d by the antagonist of group I and II mGluRs (S)-alpha-methyl-4-carboxyphen ylglycine. Membrane depolarizations and intracellular Ca2+ rises were block ed 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 a lso necessary. These data suggest that oscillatory responses generated by g roup 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 e voked only smaller depolarizations and intracellular Ca2+ rises, with no os cillations, in other hippocampal interneurons located in or near stratum la cunosum-moleculare. Thus mGluR-mediated oscillatory responses are specifica lly expressed in certain interneuron subtypes. This heterogeneous expressio n of glutamate and Ca2+ signaling pathways in specific interneurons may be relevant to their selective vulnerability to excitotoxicity.