Ca2+ Oscillations Mediated by the Synergistic Excitatory Actions of GABAA 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.

Single-Cell Characterization of Retrograde Signaling by Brain-Derived Neurotrophic Factor

“…In isolated hippocampal slice preparations, the resting potential in the cell bodies of immature pyramidal neurons has been reported to be approximately Ϫ85 mV in quiescent cells in which activity has been blocked (Leinekugel et al, 1997;Fricker et al, 1999); without blocking activity, this value decreased to Ϫ77 mV (Tyzio et al, 2003). In this case, is the BDNF secretion that we observe likely to occur in vivo?…”

Hippocampal Theta in the Newborn Rat Is Revealed under Conditions That Promote REM Sleep

“…Interest in developmental aspects of the anatomy and function of this structure is increasing. Most recently, in vitro investigations of neonatal rat hippocampal activity have demonstrated the presence of synchronous giant depolarizing potentials (GDPs) (Leinekugel et al, 1997;Garaschuk et al, 1998). Based on in vivo evidence that rats younger than 8 d of age do not exhibit hippocampal theta activity (Leblanc and Bland, 1979;Leinekugel et al, 2002) but do exhibit hippocampal sharp waves (SPWs) that resemble the GDPs found in vitro (Leinekugel et al, 2002), it has been suggested that SPWs "represent the major source of correlated neuronal activity for the neonatal hippocampus" (Leinekugel et al, 2002).…”

GABA-mediated giant depolarizing potentials as coincidence detectors for enhancing synaptic efficacy in the developing hippocampus

“…This switch appears to be regulated by GABA because it can be prevented by blocking GABA A receptors and accelerated by increasing GABA A receptor activation (9), thus suggesting a prominent role of GABA signaling during postnatal development (10). The depolarizing action of GABA during GDPs results in calcium influx through the activation of Nmethyl-D-aspartate (NMDA) receptors and voltage-dependent calcium channels (11)(12)(13). Thus, as in many others developing systems (14)(15)(16)(17), GDPs ensure large calcium oscillations even in neurons with few synapses (6, 13).…”