Depolarizing GABAergic mechanisms of hippocampal seizure-like activity in post-tetanic and low-Mg2+ conditions

Abstract

GABA is known to be a major inhibitory neurotransmitter in mature mammalian brains. However, the effect of GABA can be converted into depolarizing or even excitatory when the postsynaptic Cl⁻ concentration becomes relatively high. We have recently shown that seizure-like afterdischarge induced by tetanic stimulation in normal ACSF (post-tetanic afterdischarge) is mediated by GABAergic excitation in mature hippocampal CA1 pyramidal cells. Here we investigated the possible contribution of similar depolarizing/excitatory GABAergic input to seizure-like afterdischarge induced in a low extracellular Mg²⁺ condition, as another experimental seizure model (low-Mg²⁺ afterdischarge). Perfusion of GABA_A antagonists abolished low-Mg²⁺ afterdischarge in most cases. Each oscillatory response during low-Mg²⁺ afterdischarge was dependent on Cl⁻ conductance and contained an F⁻-insensitive depolarizing component in the pyramidal cells. Perforated patch-clamp recordings revealed that GABA responses were indeed depolarizing during low-Mg²⁺ afterdischarge. Moreover, interneurons in the strata pyramidale and oriens discharged in oscillatory cycles more actively than those in other layers. These results suggest that the depolarizing GABAergic input may facilitate oscillatory synchronization among hippocampal CA1 pyramidal cells during low-Mg²⁺ afterdischarge in a fashion similar to the expression of post-tetanic afterdischarge. [J Physiol Sci. 2006;56 Suppl:S167]