Effects of Diazepam on Low-Frequency and High-Frequency Electrocortical γ-Power Mediated by α1- and α2-GABA_A...

Patterns of spontaneous electric activity in the cerebral cortex change upon administration of benzodiazepines. Here we are testing the hypothesis that the prototypical benzodiazepine, diazepam, affects spectral power density in the low (20-50 Hz) and high (50-90 Hz) γ-band by targeting GABA_A receptors harboring α₁- and α₂-subunits. Local field potentials (LFPs) and action potentials were recorded in the barrel cortex of wild type mice and two mutant strains in which the drug exclusively acted via GABA_A receptors containing either α₁- (DZα₁-mice) or α₂-subunits (DZα₂-mice). In wild type mice, diazepam enhanced low γ-power. This effect was also evident in DZα₂-mice, while diazepam decreased low γ-power in DZα₁-mice. Diazepam increased correlated local LFP-activity in wild type animals and DZα₂- but not in DZα₁-mice. In all genotypes, spectral power density in the high γ-range and multi-unit action potential activity declined upon diazepam administration. We conclude that diazepam modifies low γ-power in opposing ways via α1- and α2-GABA_A receptors. The drug's boosting effect involves α2-receptors and an increase in local intra-cortical synchrony. Furthermore, it is important to make a distinction between high- and low γ-power when evaluating the effects of drugs that target GABA_A receptors.