title: Ca2+ oscillations mediated by the synergistic excitatory actions of GABA(A) and NMDA receptors in the neonatal hippocampus.
abstract: 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.
authors.affiliation: INSERM Unité 29, Hôpital de Port-Royal, Paris, France.
authors.forename: X
authors.initials: X
authors.lastname: Leinekugel
authors.forename: I
authors.initials: I
authors.lastname: Medina
authors.forename: I
authors.initials: I
authors.lastname: Khalilov
authors.forename: Y
authors.initials: Y
authors.lastname: Ben-Ari
authors.forename: R
authors.initials: R
authors.lastname: Khazipov
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000502:physiology*; D015220:Calcium Channels / Q000502:physiology; D058785:GABA-A Receptor Agonists; D006624:Hippocampus / Q000502:physiology*; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects; D007539:Isonicotinic Acids / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials; D009473:Neuronal Plasticity; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D013569:Synapses / Q000502:physiology
chemical_list: D015220:Calcium Channels; D058785:GABA-A Receptor Agonists; D007539:Isonicotinic Acids; D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate; D008274:Magnesium; D002118:Calcium; C015300:isoguvacine