Glutamate Controls the Induction of GABA-Mediated Giant Depolarizing Potentials Through AMPA Receptors in Neonatal Rat Hippocampal Slices

Abstract

Glutamate controls the induction of GABA-mediated giant depolarizing potentials through AMPA receptors in neonatal rat hippocampal slices. Giant depolarizing potentials (GDPs) are generated by the interplay of the depolarizing action of GABA and glutamate. In this study, single and dual whole cell recordings (in current-clamp configuration) were performed from CA3 pyramidal cells in hippocampal slices obtained from postnatal (P) days P1- to P6-old rats to evaluate the role of ionotropic glutamate receptors in GDP generation. Superfusion of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) (10-40 microM) completely blocked GDPs. However, in the presence of CNQX, it was still possible to re-induce the appearance of GDPs with GABA (20 microM) or (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxadepropionate (AMPA) (5 microM). This effect was prevented by the more potent and selective AMPA receptor antagonist GYKI 53655 (50-100 microM). In the presence of GYKI 53655, both kainic or domoic acid (0.1-1 microM) were unable to induce GDPs. In contrast, bath application of D-(-)-2-amino-5-phosphonopentanoic acid (50 microM) or (+)-3-(2carboxy-piperazin-4-yl)-propyl-L-phosphonic acid (20 microM) produced only a 37 +/- 9% (SE) and 36 +/- 11% reduction in GDPs frequency, respectively. Cyclothiazide, a selective blocker of AMPA receptor desensitization, increased GDP frequency by 76 +/- 14%. Experiments were also performed with an intracellular solution containing KF to block GABAA receptor-mediated responses. In these conditions, a glutamatergic component of GDP was revealed. GDPs could still be recorded synchronous with those detected simultaneously with KCl-filled electrodes, although their amplitude was smaller. Similar results were found in pair recordings obtained from minislices containing only a small portion of the CA3 area. These data suggest that GDP generation requires activation of AMPA receptors by local release of glutamate from recurrent collaterals.

Compensatory Enhancement of Intrinsic Spiking upon NKCC1 Disruption in Neonatal Hippocampus

“…Ϫ/Ϫ slices In agreement with previous data from rat slices (Bolea et al, 1999;Lamsa et al, 2000), exposure of WT mouse slices to the AMPA/ kainate blocker NBQX (10 -50 M) resulted in a near-complete inhibition of fGDP frequency to 9.2 Ϯ 3.4% (median, 6.5%; range, 0 -26%) of control (n ϭ 9; p ϭ 0.00017) (Fig. 4 A).…”

“…The finding that neonatal NKCC1 Ϫ/Ϫ slices generate GABAergic bursts that are similar to those seen in the wild-type mouse (Fig. 2 A) supports the view that the interneuronal network events are a consequence, and not a cause, of GDPs (Bolea et al, 1999;Sipilä et al, 2005).…”

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

“…It is worth noting that nifedipine, CPP, and D-AP5 did not alter the shape or the amplitude of GDPs (data not shown; see also ref. 3).…”

“…They have been recorded also in the intact brain of rat pups, where they occur at the same frequency as in acute slices (0.3-0.1 Hz) during immobility periods, sleep, and feeding (2). GDPs depend on the synergistic action of ␥-aminobutyric acid (GABA) and glutamate acting on GABA A and (RS)-␣-amino-3-hydroxy-5-methyl-4-isoxadepropionate (AMPA) receptors, respectively (1,3). Early in postnatal life, GABA depolarizes and excites the postsynaptic cells (4)(5)(6) because of high intracellular [Cl Ϫ ], which results mainly from the unbalance of two Cl Ϫ cotransporter systems, the NKCCl and KCC2 that enhance and lower intracellular [Cl Ϫ ], respectively (7).…”

Endogenous Activation of Kainate Receptors Regulates Glutamate Release and Network Activity in the Developing Hippocampus

“…In the neonatal hippocampus, spontaneous network bursts are seen both in vitro (Ben-Ari et al, 1989;Garaschuk et al, 1998;Palva et al, 2000) and in vivo (Lahtinen et al, 2002;Leinekugel et al, 2002). This activity consists of glutamate receptor (GluR)-driven synchronous bursts, which are rhythmically paced by GABA A receptor-mediated conductances (Khazipov et al, 1997;Bolea et al, 1999;Lamsa et al, 2000).…”