Diazepam and ethanol differently modulate neuronal activity in organotypic cortical cultures

• Published in: BMC neuroscience 2019-12, Vol.20 (1), p.58-58, Article 58
• Main Authors: Kreuzer, Matthias, García, Paul S, Brucklacher-Waldert, Verena, Claassen, Rebecca, Schneider, Gerhard, Antkowiak, Bernd, Drexler, Berthold
• Format: Article
• Language: English
• Subjects: Action potential; Action Potentials - drug effects; Analysis; Anesthesia; Animals; Antianxiety agents; Benzodiazepines; Biological activity; Brain; Brain slice preparation; Calcium channels; Central nervous system depressants; Central Nervous System Depressants - pharmacology; Diazepam; Diazepam - pharmacology; Electrophysiological recording; Ethanol; Ethanol - pharmacology; Evaluation; Experiments; Female; Firing pattern; GABA Modulators - pharmacology; GABAA receptors; Male; Neocortex; Neocortex - drug effects; Neocortex - physiology; Neurons - drug effects; Neurons - physiology; Pharmacodynamics; Rats, Sprague-Dawley; Tissue Culture Techniques; γ-Aminobutyric acid A receptors
• ISSN: 1471-2202; 1471-2202
• DOI: 10.1186/s12868-019-0540-6

The pharmacodynamic results of diazepam and ethanol administration are similar, in that each can mediate amnestic and sedative-hypnotic effects. Although each of these molecules effectively reduce the activity of central neurons, diazepam does so through modulation of a more specific set of receptor targets (GABA 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. 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, n = 7) or ethanol (30 and 60 mM, n = 11) 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. While both substances seem to decrease neocortical action potential firing in a not significantly different (p = 0.659, Mann-Whitney U) fashion, diazepam increases the spectral power of the up-state without significantly impacting the spectral composition, whereas ethanol does not significantly change the spectral power but the oscillatory architecture of the up-state as revealed by the Friedman test with Bonferroni correction (p