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

Xavier Leinekugel, Igor Medina, Ilgam Khalilov, Yehezkel Ben-Ari, Roustem Khazipov
Neuron. 1997-02-01; 18(2): 243-255
DOI: 10.1016/S0896-6273(00)80265-2

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

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

Leinekugel X(1), Medina I, Khalilov I, Ben-Ari Y, Khazipov R.

Author information:
(1)INSERM Unité 29, Hôpital de Port-Royal, Paris, France.

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.

DOI: 10.1016/s0896-6273(00)80265-2
PMID: 9052795 [Indexed for MEDLINE]

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