The Journal of Neurophysiology Vol. 79 No. 2 February 1998, pp. 659-669
Copyright ©1998 The American Physiological Society

Transient Suppression of GABA_A-Receptor-Mediated IPSPs After Epileptiform Burst Discharges in CA1 Pyramidal Cells

F.E.N. Le Beau and B. E. Alger

Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland 21201

Le Beau, F.E.N. and B. E. Alger. Transient suppression ofGABA_A-receptor-mediated IPSPs after epileptiform burst discharges in CA1 pyramidal cells. J. Neurophysiol. 79: 659-669, 1998. Epileptiform burst discharges were elicited in CA1 hippocampal pyramidal cells in the slice preparation by perfusion with Mg²⁺-free saline. Intracellular recordings revealed paroxysmal depolarization shifts (PDSs) that either occurred spontaneously or were evoked by stimulation of Schaffer collaterals. These bursts involved activation of N-methyl-D-aspartate receptors because burst discharges were reduced or abolished by DL-2-amino-5-phosphonovaleric acid. Bath application of carbachol caused an increase in spontaneous activity that was predominantly due to -aminobutyric acid-A-receptor-mediated spontaneous inhibitory postsynaptic potentials (sIPSPs). A marked reduction in sIPSPs (31%) was observed after each epileptiform burst discharge, which subsequently recovered to preburst levels after ~4-20 s. This sIPSP suppression was not associated with any change in postsynaptic membrane conductance. A suppression of sIPSPs also was seen after burst discharges evoked by brief (100-200 ms) depolarizing current pulses. N-ethylmaleimide, which blocks pertussis-toxin-sensitive G proteins, significantly reduced the suppression of sIPSPs seen after a burst response. When increases in intracellular Ca²⁺ were buffered by intracellular injection of ethylene glycol bis(-aminoethyl)ether-N,N,N,N-tetraacetic acid, the sIPSP suppression seen after a single spontaneous or evoked burst discharge was abolished. Although we cannot exclude other Ca²⁺-dependent mechanisms, this suppression of sIPSPs shared many of the characteristics of depolarization-induced suppression of inhibition (DSI) in that it involved activation of G proteins and was dependent on increases in intracellular calcium. These findings suggest that a DSI-like process may be activated by the endogenous burst firing of CA1 pyramidal neurons.

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