Comparable GABAergic mechanisms of hippocampal seizurelike activity in posttetanic and low-Mg2+ conditions

Abstract

It is known that GABA is a major inhibitory neurotransmitter in mature mammalian brains, but the effect of this substance is sometimes converted into depolarizing or even excitatory when the postsynaptic Cl- concentration becomes high. Recently we have shown that seizurelike afterdischarge induced by tetanic stimulation in normal extracellular fluid (posttetanic afterdischarge) is mediated through GABAergic excitation in mature hippocampal CA1 pyramidal cells. In this study, we examined the possible contribution of similar depolarizing/excitatory GABAergic input to the CA1 pyramidal cells to the seizurelike afterdischarge induced in a low extracellular Mg2+ condition, another experimental model of epileptic seizure activity (low-Mg2+ afterdischarge). Perfusion of the GABAA antagonist bicuculline abolished the low-Mg2+ afterdischarge, but not the interictal-like activity, in most cases. Each oscillatory response during the low-Mg2+ afterdischarge was dependent on Cl- conductance and contained an F- -insensitive depolarizing component in the pyramidal cells, thus indicating that the afterdischarge response may be mediated through both GABAergic and nonGABAergic transmissions. In addition, local GABA application to the recorded cells revealed that GABA responses were indeed depolarizing during the low-Mg2+ afterdischarge. Furthermore, the GABAergic interneurons located in the strata pyramidale and oriens fired in oscillatory cycles more actively than those in other layers of the CA1 region. These results suggest that the depolarizing GABAergic input may facilitate oscillatory synchronization among the hippocampal CA1 pyramidal cells during the low-Mg2+ afterdischarge in a manner similar to the expression of the posttetanic afterdischarge.