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

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Abstract
Le Beau, F.E.N. and B. E. Alger. Transient suppression ofGABAA-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 γ-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(β-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.