Quantification of short-term slow wave sleep homeostasis and its disruption by minocycline in the laboratory mouse.

Electroencephalographic slow wave activity (SWA) during slow wave sleep (SWS) undergoes dynamic fluctuations in reaction to sleep/wake history. SWA increases as a consequence of prior waking and decreases as consequence of prior SWS. These fluctuations are evidence for a homeostatic regulatory process, the neurobiological underpinnings of which remain to be defined. The anti-neuroinflammatory agent minocycline abolishes the increase in SWA that normally occurs after 1- or 3-h sleep deprivation. We sought to determine whether this effect is also observed during spontaneous sleep. We describe a novel procedure for measuring the predictive relationship between spontaneous changes in sleep/wake states in the short-term (less than 30 min) and subsequent SWA. In saline-treated mice, 16 or more minutes of spontaneous wakefulness during a 20-min interval causes an increase in SWA during subsequent SWS, and 16 or more minutes spent in SWS causes a decrease in SWA during subsequent SWS. Minocycline administration (45 mg/kg) abolishes the increase caused by wakefulness but not the decrease caused by sleep. These data demonstrate that minocycline attenuates SWA dynamics in spontaneous sleep. Inflammatory events in the brain may underlie, in part, wakefulness-induced changes in the sleep electroencephalogram.