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
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