Synaptic and intrinsic mechanisms shape synchronous oscillations in hippocampal neurons in culture

Abstract

We have detected spontaneous, synchronous calcium oscillations, associated with variations in membrane potential, in hippocampal neurons maintained in primary culture. The oscillatory activity is synaptically driven, as it is blocked by tetrodotoxin, by the glutamate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and by toxins inhibiting neurotransmitter release from presynaptic nerve endings. Neuronal oscillations do not require for their expression the presence of a polyneuronal network and are not primarily influenced by the gamma-aminobutyric acid (GABA(A)) receptor antagonist picrotoxin, suggesting that they entirely rely on glutamatergic neurotransmission. Synaptic and intrinsic conductances shape the synchronized oscillations in hippocampal neurons. The concomitant activation of N-methyl-D-aspartate (NMDA) receptors and voltage-activated L-type calcium channels allows calcium entering from the extracellular medium and sustaining the long depolarization, which shapes every single calcium wave.