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

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)-α-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.