Effects of Anesthesia on the Response to Sleep Deprivation

SLEEP IS HOMEOSTATICALLY REGULATED IN THAT SLEEP NEED INCREASES WITH TIME SPENT AWAKE AND DECREASES DURING SLEEP. THE BEST characterized marker of sleep homeostasis is SWA, the EEG power between 0.5-4.0 Hz during NREM sleep. In birds and mammals NREM SWA reaches an apex at the beginning of the sleep period and decreases with time spent asleep.1–3 Moreover, staying awake from ∼3 to ∼24 hours results in progressively higher SWA levels at sleep onset, while naps during the day reduce SWA the following night.4,5 Usually recorded from the scalp via the EEG, SWA reflects synchronous firing of large neuronal populations that are coordinated by an underlying slow oscillation, the fundamental cellular phenomenon of NREM sleep.6,7 Increasing evidence suggests that slow waves are more than just an epiphenomenon of NREM sleep. In fact, they can mediate some of sleep's beneficial effects. For instance, intermittent transcranial direct current stimulation during early NREM sleep, which temporarily increased SWA, was found to enhance retention in a paired-associate memory task.8 Moreover, pharmacological enhancement of slow wave sleep reduces cognitive impairments associated with sleep restriction.9,10 Finally, two recent studies showed that the selective suppression of slow waves using acoustic stimuli (without waking up the subjects) prevented post-sleep improvement in performance after visual texture discrimination learning11 and visuomotor learning.12 Thus, it seems that slow waves may benefit several aspects of performance, from the prevention of cognitive impairments to memory consolidation. Much work has been done to characterize the role of slow waves in sleep homeostasis, and it has been demonstrated that the occurrence of slow waves during NREM sleep is necessary to reduce sleep need.13 However, slow waves are not exclusive to sleep states and, in fact, the slow oscillation was first reported simultaneously in anesthetized cats and sleeping humans.14 Indeed, many anesthetics used in the clinic, including the volatile anesthetics isoflurane (ISO) and desflurane (DES) and the intravenous agent propofol produce, at relatively low concentrations, a NREM-like EEG activity dominated by slow waves, while higher concentrations lead to an isoelectric tracing which lacks slow waves.15 However, whether slow waves as induced by anesthetics affect the homeostatic regulation of sleep remains largely unexplored. In humans a 3-h period of low concentration ISO in the morning was found to reduce the percentage of time spent in slow wave sleep during the subsequent night,16 suggesting that sleep pressure may have been reduced by anesthesia. However, the EEG was not recorded during anesthesia, and thus whether continuous slow waves were indeed present was not confirmed. Moreover, ISO was administered in the morning, when the sleep pressure was presumably low, and 75% of the subjects were allowed to take naps, making the interpretation of the subsequent reduction in slow wave sleep quite difficult. In a more recent study, rats were sleep deprived for 24 h and then anesthetized with propofol for 6 h.17 After recovery from anesthesia, the duration of NREM and REM sleep decreased, and SWA did not show the rebound normally expected after prolonged sleep loss. However, rats were allowed to recover during the dark phase, when they are normally active. Moreover, because of filter settings, only the high range (2-4 Hz) SWA was analyzed. Several studies found that the SWA rebound after sleep deprivation is either most prominent,18 longer lasting,19,20 or even limited to its lowest frequency range.21 Thus, it is important to assess whether anesthesia affects low range sleep SWA. Finally, a recent study found that 4 h of ISO anesthesia (presumably with slow waves) does not affect the REM sleep rebound after selective REM sleep deprivation for 24 h, but NREM sleep and SWA were not studied.22 The goal of this study was to determine whether 1 hour of anesthesia characterized by continuous slow waves reduces the sleep pressure previously created by a period of total sleep deprivation. To this end rats were sleep deprived for 4 h starting at light onset, anesthetized for 1 hour, and then allowed to recover during the light phase, when they normally sleep. Moreover, we wanted to determine whether the effects on recovery sleep differ when the dose of anesthetic is increased to induce isoelectric EEG with few slow waves.