Differential effects of iontophoretic application of the GABA A-antagonists bicuculline and gabazine on tone-evoked local field potentials in primary auditory cortex: Interaction with ketamine anesthesia

Abstract

γ-Aminobutric acid (GABA) is one of the main inhibitory transmitters in the central nervous system. In a recent study we have demonstrated differential effects of two iontophoretically applied GABA A-blockers, bicuculline (BIC) and gabazine (SR 95531), on neuronal responses in primary auditory cortex (AI): Whereas the only effect of gabazine was to block GABA A-mediated inhibition, BIC application additionally induced dose-dependent side effects, probably on calcium-dependent potassium channels. Here we investigated the effects of the two drugs on pure tone-evoked local field potentials (LFPs) in AI. In contrast to spiking activity, which reflects neuronal output, LFP are believed to mainly reflect dendritic activity and therefore neuronal input. LFPs were recorded from the left AI of anaesthetized and unanaesthetized Mongolian gerbils before, during and after microiontophoretic application of BIC and gabazine using multi-barrel glass electrodes. After the application of both drugs, a significant increase of the amplitude of the N1 component of the LFP was observed in both anaesthetized and unanaesthetized animals, but this increase was significantly more pronounced after BIC than after gabazine application, a result which corresponds to the effects on neuronal discharge rate reported earlier. In contrast, the effects of BIC and gabazine on LFP duration (prolongation) and LFP spectral tuning (sharpening) were affected by ketamine anesthesia, an effect that was not seen in the spiking data. We conclude from the data presented that the main functional role of GABA A-mediated inhibition in auditory cortex is to (1) prevent over-excitation (seizures) of cortical networks and (2) to speed up cortical processing.