Novel Modulatory Effects of Neurosteroids and Benzodiazepines on Excitatory and Inhibitory Neurons Excitability: A Multi-Electrode Array Recording Study

The study explored the effects of neurosteroids (THDOC and ALLO) and benzodiazepines (Clonazepam and Midazolam) on neuronal excitability using multi-electrode array recordings in cultured mouse neocortex networks. Both neurosteroids and benzodiazepines decreased neuronal firing at low concentrations, with THDOC and ALLO inducing long-lasting changes in network connectivity similar to long-term depression (LTD). THDOC specifically caused a persistent depression of inhibitory neuron firing, while ALLO affected both excitatory and inhibitory neurons. Clonazepam and Midazolam also reduced excitability, with Midazolam causing a lasting depression of inhibitory neurons. The study highlighted the significant regulatory role of these compounds on network activity, emphasizing their potential impact on neuronal firing modes and connectivity.