Perpetual inhibitory activity in mammalian brain slices generated by spontaneous GABA release (original) (raw)

Miniature spontaneous inhibitory postsynaptic currents (slPSCs) mediated by GABA A receptors were recorded using whole-cell patch clamp recordings in rat brain slices maintained in vitro at 34 _+ 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/tM tetrodotoxin (TrX). 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-(Eo). Generally, 70-80 mV away from E a, 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.