Ca2+ oscillations mediated by the synergistic excitatory actions of GABA(A) and NMDA receptors in the neonatal hippocampus

Neuron. 1997 Feb;18(2):243-55. doi: 10.1016/s0896-6273(00)80265-2.


We asked whether GABA(A) and NMDA receptors may act in synergy in neonatal hippocampal slices, at a time when GABA exerts a depolarizing action. The GABA(A) receptor agonist isoguvacine reduced the voltage-dependent Mg2+ block of single NMDA channels recorded in cell-attached configuration from P(2-5) CA3 pyramidal neurons and potentiated the Ca2+ influx through NMDA channels. The synaptic response evoked by electrical stimulation of stratum radiatum was mediated by a synergistic interaction between GABA(A) and NMDA receptors. Network-driven Giant Depolarizing Potentials, which are a typical feature of the neonatal hippocampal network, provided coactivation of GABA(A) and NMDA receptors and were associated with spontaneous and synchronous Ca2+ increases in CA3 pyramidal neurons. Thus, at the early stages of development, GABA is a major excitatory transmitter that acts in synergy with NMDA receptors. This provides in neonatal neurons a hebbian stimulation that may be involved in neuronal plasticity and network formation in the developing hippocampus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / physiology
  • Animals
  • Animals, Newborn
  • Calcium / physiology*
  • Calcium Channels / physiology
  • GABA-A Receptor Agonists
  • Hippocampus / physiology*
  • In Vitro Techniques
  • Ion Channel Gating / drug effects
  • Isonicotinic Acids / pharmacology
  • Magnesium / pharmacology
  • Male
  • Membrane Potentials
  • Neuronal Plasticity
  • Rats
  • Rats, Wistar
  • Receptors, GABA-A / physiology*
  • Receptors, N-Methyl-D-Aspartate / physiology*
  • Synapses / physiology


  • Calcium Channels
  • GABA-A Receptor Agonists
  • Isonicotinic Acids
  • Receptors, GABA-A
  • Receptors, N-Methyl-D-Aspartate
  • Magnesium
  • Calcium
  • isoguvacine