SPONTANEOUS RELEASE OF GABA ACTIVATES GABA B RECEPTORS and CONTROLS NETWORK ACTIVITY IN THE NEONATAL RAT HIPPOCAMPUS. McLean, H.A., O. Caillard, R. Khazipov, Y. Ben-Ari and J-L Gaiarsa. Institut National de la Sant[acute]e et de la Recherche M[acute]edicale Unit[acute]e 29, H[circumflex]opital de Port-Royal, 123 Bd de Port-Royal, 75674 Paris Cedex, France.
APStracts 3:0060N, 1996.
SUMMARY AND CONCLUSIONS
1. We investigated the effects of the selective GABA B receptor antagonist, P- 3- aminopropyl-P-diethoxymethyl phosphoric acid (CGP 35348), on spontaneous and evoked postsynaptic potentials (PSPs) and currents (PSCs) in CA3 pyramidal cells and interneurons of hippocampal slices obtained between postnatal day 3 and 7 using intracellular and whole cell recording techniques. The intracellular pipette solution contained either 2M CsCl or 50 mM 2(triethylamino)-N-(2,6- dimethylphenyl) acetamine (QX314) dissolved in 2M KMeSO 4 . Cesium and QX314 block postsynaptic responses mediated by GABA B receptors. 2. Under control conditions, bath application of CGP 35348 (0.5 - 1 mM) progressively increased the duration of spontaneous and evoked polysynaptic giant GABAergic PSPs leading to the appearance of ictal-like discharges. The effects of CGP 35348 were dose-dependent and voltage- independent. 3. In CA3 pyramidal neurons, CGP 35348 (0.5 mM) had no effect on monosynaptic GABAergic IPSPs that were isolated in the presence of ionotropic glutamate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 [mu]M) and D(-)2-amino-5-phosphovaleric acid (D-APV, 50 [mu]M). Similarly, CGP 35348 (0.5 mM) had no effect on monosynaptic glutamatergic EPSPs that were isolated in the presence of bicuculline (10 [mu]M) and high divalent cation ACSF (6 mM Mg 2+ /4 mM Ca 2+ ). 4. In CA3 pyramidal neurons exposed to CNQX (20 [mu]M) and D-APV (50 [mu]M), application of the potassium channel blocker 4-aminopyridine (4-AP, 50 [mu]M) generated synchronous giant GABAergic PSPs that were blocked in the presence of high divalent cation ACSF (6 mM Mg 2+ /4 mM Ca 2+ ) or bicuculline (10 [mu]M). The duration of these synchronous GABAergic PSPs was prolonged in the presence of CGP 35348 (0.5 mM) but did not lead to the appearance of ictal-like discharges. 5. In the presence of bicuculline, interictal giant glutamatergic potentials were observed in simultaneously recorded CA3 pyramidal cells and interneurons. CGP 35348 (0.5 mM) progressively increased the duration of these bicuculline- induced glutamatergic bursts leading to the simultaneous appearance of ictal discharges in both pyramidal cells and interneurons. 6. These results suggest that in the neonatal CA3 hippocampal region, when synchronous giant polysynaptic GABAergic PSPs are present (i.e. under basal, control conditions), spontaneously released GABA reaches a critical level and activates GABA B receptors on both pyramidal cells and interneurons thus regulating the level of glutamatergic and GABAergic activity in the CA3 neuronal network.

Received 14 August 1995; accepted in final form 12 March 1996.
APS Manuscript Number J531-5.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 27 March 96