Effects of Diazepam on Low-Frequency and High-Frequency Electrocortical gamma-Power Mediated by alpha 1-and alpha 2-GABA(A) Receptors

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) gamma-band by targeting GABA(A) receptors harboring alpha(1)- and alpha(2)-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 alpha(1)- (DZ alpha(1)-mice) or alpha(2)-subunits (DZ alpha(2)-mice). In wild type mice, diazepam enhanced low gamma-power. This effect was also evident in DZ alpha(2)-mice, while diazepam decreased low gamma-power in DZ alpha(1)-mice. Diazepam increased correlated local LFP-activity in wild type animals and DZ alpha(2)- but not in DZ alpha(1)-mice. In all genotypes, spectral power density in the high gamma-range and multi-unit action potential activity declined upon diazepam administration. We conclude that diazepam modifies low gamma-power in opposing ways via alpha(1)- and alpha(2)-GABA(A) receptors. The drug's boosting effect involves alpha(2)-receptors and an increase in local intra-cortical synchrony. Furthermore, it is important to make a distinction between high- and low gamma-power when evaluating the effects of drugs that target GABA(A) receptors.