Synchronized oscillations in hippocampal CA3 neurons induced by metabotropic glutamate receptor activation

Abstract

The metabotropic glutamate receptor agonist (1S,3R)-1-aminocyclopentane- 1,3 dicarboxylic acid (ACPD) at concentrations above 60 μM produced stereotypic oscillatory activity in CA3 pyramidal cells of rat hippocampal slices. This oscillatory activity consisted of trains of depolarizations with overriding action potentials. On average, individual trains lasted 7 sec and recurred at intervals of 24 sec. During each train, the constituent depolarizations achieved a maximum frequency of 27 Hz, then slowed to 8 Hz toward the end of the train. Extracellular and dual intracellular recordings suggested that this ACPD-induced oscillatory activity occurred synchronously in the CA3 population. The oscillations persisted in the presence of GABA(A), GABA(B1) and NMDA receptor antagonists. In contrast, the oscillations were blocked by the AMPA/kainate receptor antagonist 6-cyano-7-nitroquinoxaline- 2,3-dione (CNQX; 10-30 μM). Likewise, the oscillations were blocked by the metabotropic glutamate receptor antagonists (+)-α-methyl-4- carboxyphenylglycine [(+)-MCPG; 1 mM], (s)-4-carboxy-3-hydroxyphenylglycine [(S)-4C3HPG; 1 mM] and (s)-4-carboxyphenylglycine [(S)-4CPG; 1 mM]. The results suggest that activation of metabotropic glutamate receptors can result in a permissive state that allows AMPA/kainate receptor-mediated conductances to mediate synchronized activity among hippocampal CA3 neurons.