Perpetual inhibitory activity in mammalian brain slices generated by spontaneous GABA release

Abstract

Miniature spontaneous inhibitory postsynaptic currents (sIPSCs) mediated by GABA_A receptors were recorded using whole-cell patch clamp recordings in rat brain slices maintained in vitro at34 ± 1 °C. We have found that firing of action potentials by principal neurons or by GABAergic interneurons is not necessary to the generation of sIPSCs since they persist in the presence of 1–5 μM tetrodotoxin (TTX). The average frequency of the discrete sIPSCs exhibits a large cell-to-cell variability and is between 5–15 Hz. The amplitudes of the sIPSCs depend on the difference between the membrane potential and the equilibrium potential for Cl⁻ (E_Cl). Generally, 70–80 mV away from E_Cl, sIPSCs have a mean amplitude of 30–80 pA (i.e. peak conductance of 400–1000 pS) with an average decay time constant of 5.8 ms. Accordingly, unitary single sIPSCs arise from the simultaneous activation of no more than 20 GABA_A receptor/channels. The perpetual barrage of spontaneous GABAergic activity is very likely to be a critical factor in the regulation of neuronal excitability and the mechanism of action of several neuroactive compounds.