Diazepam and ethanol differently modulate neuronal activity in organotypic cortical cultures
Abstract Background: The pharmacodynamic results of diazepam and ethanol administration are similar, in that each can mediate amnestic, sedative-hypnotic effects. Although each of these molecules effectively reduces the activity of central neurons, diazepam does so through modulation of a more specific set of receptor targets (GABAA receptors containing a γ-subunit), while alcohol is less selective in its receptor bioactivity. Our investigation focuses on divergent actions of diazepam and ethanol on the firing patterns of cultured cortical neurons. Method: We used electrophysiological recordings from organotypic slice cultures derived from Sprague-Dawley rat neocortex. We exposed these cultures to either diazepam (15 and 30 µM) or ethanol (30 and 60 mM) and recorded the electrical activity at baseline and experimental conditions. For analysis, we extracted the episodes of spontaneous activity, i.e., cortical up-states. After separation of action potential and local field potential (LFP) activity, we looked at differences in the number of action potentials, in the spectral power of the LFP, as well as in the coupling between action potential and LFP phase. Results: While both substances seem to decrease neocortical action potential firing in a similar fashion, diazepam seems to increase the spectral power of the up-state without impacting the spectral composition, whereas ethanol does not change the spectral power but the oscillatory architecture of the up-state. Further, the action potential to LFP-phase coupling reveals a synchronizing effect of diazepam and a (rather weak) de-synchronizing effect for ethanol. Conclusion: Diazepam and ethanol, induce specific patterns of network depressant actions. Diazepam, via gamma subunit containing GABAA receptors, induces cortical network inhibition and increased synchronicity. Ethanol, via a wider span of molecular targets, also induces cortical network inhibition, but without an increase in synchronicity.