Diazepam effects on local cortical neural activity during sleep in mice

Abstract GABA-ergic neurotransmission plays a key role in sleep regulatory mechanisms and in brain oscillations during sleep. Benzodiazepines such as diazepam are known to induce sedation and promote sleep, however, EEG spectral power in slow frequencies is typically reduced after benzodiazepines or similar compounds. EEG slow waves arise from a synchronous alternation between periods of cortical network activity (ON) and silence (OFF), and represent a sensitive marker of preceding sleep-wake history. Yet it remains unclear how benzodiazepines act on cortical neural activity during sleep. To address this, we obtained chronic recordings of local field potentials and multiunit activity (MUA) from deep cortical layers of the primary motor cortex in freely behaving mice after diazepam injection. We found that the amplitude of individual LFP slow waves was significantly reduced after diazepam injection and was accompanied by a lower incidence and duration of the corresponding neuronal OFF periods. Further investigation suggested that this is due to a disruption in the synchronisation of cortical neurons. Our data suggest that the state of global sleep and local cortical synchrony can be dissociated, and that the brain state induced by benzodiazepines is qualitatively different from spontaneous physiological sleep.