Sleep deprivation decreases neuronal excitability and responsiveness in rats both in vivo and ex vivo.

Sleep deprivation has severe consequences for higher nervous functions. Its effects on neuronal excitability may be one of the most important factors underlying functional deterioration caused by sleep loss. In the present work, excitability changes were studied using two complementary in vivo and ex vivo models. Auditory evoked potentials were recorded from freely-moving animals in vivo. Amplitude of evoked responses showed a near-continuous decrease during deprivation. Prevention of sleep also reduced synaptic efficacy ex vivo, measured from brain slices derived from rats that underwent sleep deprivation. While seizure susceptibility was not affected significantly by sleep deprivation in these preparations, the pattern of spontaneous seizure activity was altered. If seizures developed, they lasted longer and tended to contain more spikes in slices obtained from sleep-deprived than from control rats. Current-source density analysis revealed that location and sequence of activation of local cortical networks recruited by seizures did not change by sleep deprivation. Moderate differences seen in the amplitude of individual sinks and sources might be explained by smaller net transmembrane currents as a consequence of decreased excitability. These findings contradict the widely accepted conception of synaptic homeostasis suggesting gradual increase of excitability during wakefulness. Our results also indicate that decreased neuronal excitability caused by sleep deprivation is preserved in slices prepared from rats immediately after deprivation. This observation might mean new opportunities to explore the effects of sleep deprivation in ex vivo preparations that allow a wider range of experimental manipulations and more sophisticated methods of analysis than in vivo preparations.