Duration of Sleep Inertia after Napping during Simulated Night Work and in Extended Operations

Due to the mixed findings of previous studies, it is still difficult to provide guidance on how to best manage sleep inertia after waking from naps in operational settings. One of the few factors that can be manipulated is the duration of the nap opportunity. The aim of the present study was to investigate the magnitude and time course of sleep inertia after waking from short (20-, 40- or 60-min) naps during simulated night work and extended operations. In addition, the effect of sleep stage on awakening and duration of slow wave sleep (SWS) on sleep inertia was assessed. Two within-subject protocols were conducted in a controlled laboratory setting. Twenty-four healthy young men (Protocol 1: n?=?12, mean age?=?25.1 yrs; Protocol 2: n?=?12, mean age?=?23.2 yrs) were provided with nap opportunities of 20-, 40-, and 60-min (and a control condition of no nap) ending at 02:00?h after ～20?h of wakefulness (Protocol 1 [P1]: simulated night work) or ending at 12:00?h after ～30?h of wakefulness (Protocol 2 [P2]: simulated extended operations). A 6-min test battery, including the Karolinska Sleepiness Scale (KSS) and the 4-min 2-Back Working Memory Task (WMT), was repeated every 15?min the first hour after waking. Nap sleep was recorded polysomnographically, and in all nap opportunities sleep onset latency was short and sleep efficiency high. Mixed-model analyses of variance (ANOVA) for repeated measures were calculated and included the factors time (time post-nap), nap opportunity (duration of nap provided), order (order in which the four protocols were completed), and the interaction of these terms. Results showed no test x nap opportunity effect (i.e., no effect of sleep inertia) on KSS. However, WMT performance was impaired (slower reaction time, fewer correct responses, and increased omissions) on the first test post-nap, primarily after a 40- or 60-min nap. In P2 only, performance improvement was evident 45?min post-awakening for naps of 40?min or more. In ANOVAs where sleep stage on awakening was included, the test x nap opportunity interaction was significant, but differences were between wake and non-REM Stage 1/Stage 2 or wake and SWS. A further series of ANOVAs showed no effect of the duration of SWS on sleep inertia. The results of this study demonstrate that no more than 15?min is required for performance decrements due to sleep inertia to dissipate after nap opportunities of 60?min or less, but subjective sleepiness is not a reliable indicator of this effect. Under conditions where sleep is short, these findings also suggest that SWS, per se, does not contribute to more severe sleep inertia. When wakefulness is extended and napping occurs at midday (i.e., P2), nap opportunities of 40- and 60-min have the advantage over shorter duration sleep periods, as they result in performance benefits ～45?min after waking.     

Post-Sleep Inertia Performance Benefits of Longer Naps in Simulated Nightwork and Extended Operations

Operational settings involving shiftwork or extended operations require periods of prolonged wakefulness, which in conjunction with sleep loss and circadian factors, can have a negative impact on performance, alertness, and workplace safety. Napping has been shown to improve performance and alertness after periods of prolonged wakefulness and sleep loss. Longer naps may not only result in longer-lasting benefits but also increase the risk of sleep inertia immediately upon waking. The time course of performance after naps of differing durations is thus an important consideration in weighing the benefits and risks of napping in workplace settings. The objective of this study was to evaluate the effectiveness of nap opportunities of 20, 40, or 60 min for maintaining alertness and performance 1.5–6 h post-nap in simulated nightwork (P1) or extended operations (P2). Each protocol included 12 participants in a within-subjects design in a controlled laboratory environment. After a baseline 8 h time-in-bed, healthy young males (P1 mean age 25.1 yr; P2 mean age 23.2 yr) underwent either ≈20 h (P1) or ≈30 h (P2) of sleep deprivation on four separate occasions, followed by nap opportunities of 0, 20, 40, and 60 min. Sleep on the baseline night and during the naps was recorded polysomnographically. During the nap opportunities, sleep onset latency was short and sleep efficiency was high. A greater proportion of slow-wave sleep (SWS) was obtained in nap opportunities of 40 and 60 min compared with 20 min. Rapid eye movement (REM) sleep occurred infrequently. A subjective sleepiness rating (Karolinska Sleepiness Scale, KSS), 2-Back Working Memory Task (WMT), and Psychomotor Vigilance Task (PVT) were completed 1.5, 2, 2.5, 3, 4, 5, and 6 h post-nap. The slowest 10% of PVT responses were significantly faster after 40 and 60 min naps compared with a 20 min (P1) or no (P2) nap. There were significantly fewer PVT lapses after 40 and 60 min naps compared with no nap (P2), and after 60 min naps compared with 20 min naps (P1). Participants felt significantly less sleepy and made more correct responses and fewer omissions on the WMT after 60 min naps compared with no nap (P2). Subjective sleepiness and WMT performance were not related to the amount of nap-time spent in SWS. However, PVT response speed was significantly slower when time in SWS was <10 min compared with 20–29.9 min. In conclusion, in operationally relevant scenarios, nap opportunities of 40 and 60 min show more prolonged benefits 1.5–6 h post-nap, than a 20 min or no nap opportunity. Benefits were more apparent when the homeostatic pressure for sleep was high and post-nap performance testing occurred across the afternoon (P2). For sustained improvement in cognitive performance, naps of 40–60 min are recommended. (Author correspondence: t.l.signal@massey.ac.nz)     

Athletes underestimate sleep quantity during daytime nap opportunities

ABSTRACT

This study examined the difference between athletes’ self-reported and objective sleep durations during two nap opportunities. Twelve well-trained male soccer players’ sleep durations were assessed using polysomnography and a self-report question during a 60- and 120-min nap opportunity. Participants underestimated sleep compared to objective sleep assessments for both the 60-min nap opportunity (p = 0.004) and 120-min nap opportunity (p = 0.001). Soccer players underestimated their sleep duration by approximately 10 min per hour of nap opportunity. It is yet to be determined if athletes are likely to underestimate sleep duration during their main nighttime sleep period.     

Daily Rhythms of Toxicity and Effectiveness of Anesthetics (MS222 and Eugenol) in Zebrafish (Danio Rerio)

Sleep inertia is a brief period of inferior task performance and/or disori-entation immediately after sudden awakening from sleep. Normally sleep inertia lasts <5 min and has no serious impact on conducting routine jobs. This preliminary study examined whether there are best and worst times to wake up stemming from circadian effects on sleep inertia. Since the process of falling asleep is strongly influenced by circadian time, the reverse process of awakening could be similarly affected. A group of nine subjects stayed awake for a 64-h continuous work period, except for 20-min sleep periods (naps) every 6 h. Another group of 10 subjects stayed awake for 64 h without any sleep. The differences between these two groups in performance degradation are expected to show sleep inertia on the background of sleep deprivation. Sleep inertia was measured with Baddeley's logical reasoning task, which started within 1 min of awakening and lasted for 5 min. There appeared to be no specific circadian time when sleep inertia is either maximal or minimal. An extreme form of sleep inertia was observed, when the process of waking up during the period of the circadian body temperature trough became so traumatic that it created “sleep (nap) aversion.” The findings lead to the conclusion that there are no advantages realized on sleep inertia by waking up from sleep at specific times of day.     

The Effects of a Nap Opportunity in Quiet and Noisy Environments on Driving Performance

While napping has previously been shown to alleviate the effects of sleep loss, before advocating the use of naps in transport accident campaigns it is necessary to consider whether a nap opportunity in a noisy uncomfortable environment can produce the same benefits as a nap opportunity in conditions that are conducive to sleep. To examine this, eight participants drove a driving simulator for 50 min at 11:00 h on three different test days. The simulator used has previously been found to be sensitive to the effects of sleep loss, alcohol consumption, and time of day. All three sessions were conducted after one night of sleep loss. Prior to driving during each session the participants either had a 60 min nap opportunity in a quiet or noisy environment, or no nap opportunity. Driving performance and reaction time while driving were measured, as were subjective sleepiness and ratings of sleep quality. No significant benefits of nap opportunities on driving performance were found. Levels of subjective sleepiness were not affected by the nap opportunity condition; however, sleep was rated as more refreshing and restful after a nap in a quiet environment compared to noisy environment. The measures of effect size reported suggest further research is required to unequivocally test the effects of nap opportunities on driving ability.     

The effects of a nap opportunity in quiet and noisy environments on driving performance

While napping has previously been shown to alleviate the effects of sleep loss, before advocating the use of naps in transport accident campaigns it is necessary to consider whether a nap opportunity in a noisy uncomfortable environment can produce the same benefits as a nap opportunity in conditions that are conducive to sleep. To examine this, eight participants drove a driving simulator for 50 min at 11:00 h on three different test days. The simulator used has previously been found to be sensitive to the effects of sleep loss, alcohol consumption, and time of day. All three sessions were conducted after one night of sleep loss. Prior to driving during each session the participants either had a 60 min nap opportunity in a quiet or noisy environment, or no nap opportunity. Driving performance and reaction time while driving were measured, as were subjective sleepiness and ratings of sleep quality. No significant benefits of nap opportunities on driving performance were found. Levels of subjective sleepiness were not affected by the nap opportunity condition; however, sleep was rated as more refreshing and restful after a nap in a quiet environment compared to noisy environment. The measures of effect size reported suggest further research is required to unequivocally test the effects of nap opportunities on driving ability.     

A dose-response investigation of the benefits of napping in healthy young,middle-aged and older adults

Older adults experience more fragmented sleep, greater daytime sleepiness and, nap more often than younger adults. Little research has investigated the effects of napping on waking function in older adults. In the present study, waking cognitive performance was examined in 10 young (mean age = 28 years), 10 middle-aged (mean age = 42 years) and 12 older adults (mean age = 61 years) following 60-min, 20-min and no nap conditions. It was expected that the older adults would need a longer nap to accrue benefits. Napping led to improvements for all age groups in subjective sleepiness, fatigue and accuracy on a serial addition/subtraction task. Waking electroencephalogram (EEG) confirmed that the participants were more physiologically alert following naps. There were no age differences in subjective reports or cognitive tasks; however, older adults had higher beta and gamma in the waking EEG, suggesting that they needed increased effort to maintain performance. Overall, older adults had smaller P2 amplitudes, reflecting their difficulty in inhibiting irrelevant stimuli, and delayed latencies and smaller amplitude P300s to novel stimuli, reflecting deficits in their frontal lobe functioning. Although older adults did garner benefits from napping, there was no evidence that they required longer naps to experience improvement.

     

The effects of extended nap periods on cognitive,physiological and subjective responses under simulated night shift conditions

Extended nap opportunities have been effective in maintaining alertness in the context of extended night shifts (+12?h). However, there is limited evidence of their efficacy during 8-h shifts. Thus, this study explored the effects of extended naps on cognitive, physiological and perceptual responses during four simulated, 8-h night shifts. In a laboratory setting, 32 participants were allocated to one of three conditions. All participants completed four consecutive, 8-h night shifts, with the arrangements differing by condition. The fixed night condition worked from 22h00 to 06h00, while the nap early group worked from 20h00 to 08h00 and napped between 00h00 and 03h20. The nap late group worked from 00h00 to 12h00 and napped between 04h00 and 07h20. Nap length was limited to 3 hours and 20 minutes. Participants performed a simple beading task during each shift, while also completing six to eight test batteries roughly every 2?h. During each shift, six test batteries were completed, in which the following measures were taken. Performance indicators included beading output, eye accommodation time, choice reaction time, visual vigilance, simple reaction time, processing speed and object recognition, working memory, motor response time and tracking performance. Physiological measures included heart rate and tympanic temperature, whereas subjective sleepiness and reported sleep length and quality while outside the laboratory constituted the self reported measures. Both naps reduced subjective sleepiness but did not alter the circadian and homeostatic-related changes in cognitive and physiological measures, relative to the fixed night condition. Additionally, there was evidence of sleep inertia following each nap, which resulted in transient reductions in certain perceptual cognitive performance measures. The present study suggested that there were some benefits associated with including an extended nap during 8-h night shifts. However, the effects of sleep inertia need to be effectively managed to ensure that post-nap alertness and performance is maintained.     

The effects of the preference for music on sleep inertia after a short daytime nap

Sleep and Biological Rhythms - The effects of the preference for excitative music on sleep inertia after a daytime nap were examined. Sixteen young healthy adults took a 20-min nap at 14:00 after...     

EEG power density during nap sleep: reflection of an hourglass measuring the duration of prior wakefulness

The relation between the duration of prior wakefulness and EEG power density during sleep in humans was assessed by means of a study of naps. The duration of prior wakefulness was varied from 2 to 20 hr by scheduling naps at 1000 hr, 1200 hr, 1400 hr, 1600 hr, 1800 hr, 2000 hr, and 0400 hr. In contrast to sleep latencies, which exhibited a minimum in the afternoon, EEG power densities in the delta and theta frequencies were a monotonic function of the duration of prior wakefulness. The data support the hypothesis that EEG power density during non-rapid eye movement sleep is only determined by the prior history of sleep and wakefulness and is not determined by clock-like mechanisms.     

Challenging the sleep homeostat does not influence the thermoregulatory system in men: evidence from a nap vs. sleep-deprivation study

The purpose of our study was to understand the relationship between the components of the three-process model of sleepiness regulation (homeostatic, circadian, and sleep inertia) and the thermoregulatory system. This was achieved by comparing the impact of a 40-h sleep deprivation vs. a 40-h multiple nap paradigm (10 cycles with 150/75 min wakefulness/sleep episodes) on distal and proximal skin temperatures, core body temperature (CBT), melatonin secretion, subjective sleepiness, and nocturnal sleep EEG slow-wave activity in eight healthy young men in a "controlled posture" protocol. The main finding of the study was that accumulation of sleep pressure increased subjective sleepiness and slow-wave activity during the succeeding recovery night but did not influence the thermoregulatory system as measured by distal, proximal, and CBT. The circadian rhythm of sleepiness (and proximal temperature) was significantly correlated and phase locked with CBT, whereas distal temperature and melatonin secretion were phase advanced (by 113 +/- 28 and 130 +/- 30 min, respectively; both P < 0.005). This provides evidence for a primary role of distal vasodilatation in the circadian regulation of CBT and its relationship with sleepiness. Specific thermoregulatory changes occur at lights off and on. After lights off, skin temperatures increased and were most pronounced for distal; after lights on, the converse occurred. The decay in distal temperature (vasoconstriction) was significantly correlated with the disappearance of sleep inertia. These effects showed minor and nonsignificant circadian modulation. In summary, the thermoregulatory system seems to be independent of the sleep homeostat, but the circadian modulation of sleepiness and sleep inertia is clearly associated with thermoregulatory changes.     

Sleep pattern in the starling (Sturnus vulgaris)

Electrographic and behavioural observations were conducted on two male and two female captive starlings (Sturnus vulgaris) under natural illumination conditions during autumn. Polygraphically sleep and wakefulness of starling were similar to those of other birds. Starling's total sleep (TS) and slow wave sleep (SWS) lasted 39.0 +/- 1.4% and 38.3 +/- 1.7% of the 24-h period respectively. Paradoxical sleep (PS) was 1.8 +/- 0.2% of the total sleep time. The mean durations individual of TS, SWS and PS episodes were 6.8 +/- 0.2 min, 5.0 +/- 1.0 min and 18 +/- 3 s respectively. The daily percentage of SWS was correlated with the mean episode duration while that of PS was correlated with the number of episodes rather than with the mean episode duration. Starling females spent in sleep a greater percentage of the 24-h period than males.     

Daytime naps in darkness phase shift the human circadian rhythms of melatonin and thyrotropin secretion

To systematically determine the effects of daytime exposure to sleep in darkness on human circadian phase, four groups of subjects participated in 4-day studies involving either no nap (control), a morning nap (0900-1500), an afternoon nap (1400-2000), or an evening nap (1900-0100) in darkness. Except during the scheduled sleep/dark periods, subjects remained awake under constant conditions, i.e., constant dim light exposure (36 lx), recumbence, and caloric intake. Blood samples were collected at 20-min intervals for 64 h to determine the onsets of nocturnal melatonin and thyrotropin secretion as markers of circadian phase before and after stimulus exposure. Sleep was polygraphically recorded. Exposure to sleep and darkness in the morning resulted in phase delays, whereas exposure in the evening resulted in phase advances relative to controls. Afternoon naps did not change circadian phase. These findings indicate that human circadian phase is dependent on the timing of darkness and/or sleep exposure and that strategies to treat circadian misalignment should consider not only the timing and intensity of light, but also the timing of darkness and/or sleep.     

The effect of post-lunch napping on mood,reaction time,and antioxidant defense during repeated sprint exercice

To compare the effects of two nap opportunities (20 and 90 min) to countermeasure the transient naturally occurring increased sleepiness and decreased performances during the post-lunch dip (PLD). Fourteen highly trained judokas completed in a counterbalanced and randomized order three test sessions (control (No-nap), 20- (N20) and 90-min (N90) nap opportunities). Test sessions consisted of the running-based anaerobic sprint test (RAST), simple and multiple-choice reaction times (MCRT) and the Epworth sleepiness scale (ESS). From the RAST, the maximum (P_max), mean (P_mean) and minimum (P_min) powers were calculated. Blood samples were taken before and after the RAST to measure the effect of pre-exercise napping on energetic and muscle damage biomarkers and antioxidant defense. N20 increased P_max and P_mean compared to No-nap (p < 0.001, d = 0.59; d = 0.66) and N90 (p < 0.001, d = 0.98; d = 0.72), respectively. Besides, plasma lactate and creatinine increased only when the exercise was performed after N20. Both N20 (p < 0.001, d = 1.18) and N90 (p < 0.01, d = 0.78) enhanced post-exercise superoxide dismutase activity compared to No-nap. However, only N20 enhanced post-exercise glutathione peroxidase activity (p < 0.001, d = 1.01) compared to pre-nap. Further, MCRT performance was higher after N20 compared to No-nap and N90 (p < 0.001, d = 1.15; d = 0.81, respectively). Subjective sleepiness was lower after N20 compared to No-nap (p < 0.05, d = 0.92) and N90 (p < 0.01, d = 0.89). The opportunity to nap for 20 min in the PLD enhanced RAST, MCRT performances, and antioxidant defense, and decreased sleepiness. However, the opportunity of 90 min nap was associated with decreased repeated sprint performances and increased sleepiness, probably because of the sleep inertia.     

An endogenous circadian rhythm in sleep inertia results in greatest cognitive impairment upon awakening during the biological night

Sleep inertia is the impaired cognitive performance immediately upon awakening, which decays over tens of minutes. This phenomenon has relevance to people who need to make important decisions soon after awakening, such as on-call emergency workers. Such awakenings can occur at varied times of day or night, so the objective of the study was to determine whether or not the magnitude of sleep inertia varies according to the phase of the endogenous circadian cycle. Twelve adults (mean, 24 years; 7 men) with no medical disorders other than mild asthma were studied. Following 2 baseline days and nights, subjects underwent a forced desynchrony protocol composed of seven 28-h sleep/wake cycles, while maintaining a sleep/wakefulness ratio of 1:2 throughout. Subjects were awakened by a standardized auditory stimulus 3 times each sleep period for sleep inertia assessments. The magnitude of sleep inertia was quantified as the change in cognitive performance (number of correct additions in a 2-min serial addition test) across the first 20 min of wakefulness. Circadian phase was estimated from core body temperature (fitted temperature minimum assigned 0 degrees ). Data were segregated according to: (1) circadian phase (60 degrees bins); (2) sleep stage; and (3) 3rd of the night after which awakenings occurred (i.e., tertiary 1, 2, or 3). To control for any effect of sleep stage, the circadian rhythm of sleep inertia was initially assessed following awakenings from Stage 2 (62% of awakening occurred from this stage; n = 110). This revealed a significant circadian rhythm in the sleep inertia of cognitive performance (p = 0.007), which was 3.6 times larger during the biological night (circadian bin 300 degrees , approximately 2300-0300 h in these subjects) than during the biological day (bin 180 degrees , approximately 1500-1900 h). The circadian rhythm in sleep inertia was still present when awakenings from all sleep stages were included (p = 0.004), and this rhythm could not be explained by changes in underlying sleep drive prior to awakening (changes in sleep efficiency across circadian phase or across the tertiaries), or by the proportion of the varied sleep stages prior to awakenings. This robust endogenous circadian rhythm in sleep inertia may have important implications for people who need to be alert soon after awakening.     

Sleep pattern in the rook, Corvus frugilegus

In the rook, Corvus frugilegus, electrographic and behavioural correlates of sleep and wakefulness have been determined under natural lighting conditions. Slow wave sleep (SWS) was characterized by high amplitude slow EEG activity, low neck EMG, and behavioural inactivity. Paradoxical sleep (PS) was characterized by low amplitude fast EEG activity and inconsistent decrease in EMG. PS episodes always commenced with head downward. Several eye movements occurred activity were present. The rook spent in sleep 31.8% of the 24-h period. PS however, eye movements, high tonic neck EMG activity, and behavioural activity were present. The rook spent in sleep 31.8% of the 24-h period. PS constituted 1.8% of total sleep, while the rest of total sleep was occupied by SWS. On the average, episodes of SWS and PS lasted 10.8 min and 24 s respectively. The daily percentage of SWS was highly correlated with the mean episode duration. PS amount was better correlated with the number of episodes than with their mean duration. Our data suggest that over-short period of recovery from surgery and adaptation with implanted electrodes could lead to underestimation of sleep duration in rook.     

Teen at work: the burden of a double shift on daily activities

The purpose of this study was to the evaluate time spent by working and nonworking adolescents on daily activities (work, home duties, school, transportation, other activities, leisure, sleep, and naps). Twenty-seven students, 8 male workers, 8 female workers, 5 male nonworkers, and 6 female nonworkers, ages 14-18 yrs participated in the study. They attended evening classes Monday-Friday (19:00-22:30h) in a public school in the city of S?o Paulo, Brazil. The students answered a comprehensive questionnaire on the characterization of their life, work, and health conditions. Simultaneously, they wore actigraphs (Ambulatory Monitoring, Inc.) and completed a diary of their daily activities (time spent at work, on home duties, commuting, leisure, other activities) for a minimum of 10 to a maximum of 17 consecutive days. The means of the variables were tested for differences by a two-factor (work and sex) ANOVA and Student-t test applied to pair-wise samples (weekdays and weekends). The average duration during weekdays of working time was 7 h 09 min and home duties 0 h 48 min. As for commuting time, there was a work effect [F(1,23) = 4.9; p = 0.04]; mean commuting time was 2 h 22 min for workers (males and females) and 1 h 25 min for nonworkers. There was a significant difference between workers and nonworkers [F(1,23) = 4.6; p = 0.04] regarding extra-cirricular class activities; workers spent a mean of 3 min/day on them as opposed to 1 h 14 min by nonworkers. The average daily time spent on leisure activities by workers was 6h 31 min; whereas, for nonworkers it was 7h 38min. Time spent in school amounted to 2h 47min for workers in comparison to 3h 22min by nonworkers. There was a significant work effect upon sleep [F(1,23)= 10.0; p <0.01]. The work effect upon nighttime sleep duration was significant [F(1,23)= 16.7; p <0.01]. Male workers showed a mean night sleep of 6 h 57 min and female workers 07h 15min. The average nighttime sleep duration for nonworkers was 9 h 06 min. There was a significant interactive effect between work and sex [F(1,23)= 5.6; p=0.03] for naps. Female workers showed took shortest nap on average (36 min; SD = 26 min), and female nonworkers the longest naps (1 h 45min; SD= 35min). Study and employment exert significant impact on the life and activities of high school students. Work affects sleep and nap duration plus the amount of time spent in school and other extra-curricular activities.     

Microinjection of glutamate into the pedunculopontine tegmentum induces REM sleep and wakefulness in the rat

The aim of this study was to test the hypothesis that the cells in the brain stem pedunculopontine tegmentum (PPT) are critically involved in the normal regulation of wakefulness and rapid eye movement (REM) sleep. To test this hypothesis, one of four different doses of the excitatory amino acid L-glutamate (15, 30, 60, and 90 ng) or saline (control vehicle) was microinjected unilaterally into the PPT while the effects on wakefulness and sleep were quantified in freely moving chronically instrumented rats. All microinjections were made during wakefulness and were followed by 6 h of polygraphic recording. Microinjection of 15- ng (0.08 nmol) and 30-ng (0.16 nmol) doses of L-glutamate into the PPT increased the total amount of REM sleep. Both doses of L-glutamate increased REM sleep at the expense of slow-wave sleep (SWS) but not wakefulness. Interestingly, the 60-ng (0.32 nmol) dose of L-glutamate increased both REM sleep and wakefulness. The total increase in REM sleep after the 60-ng dose of L-glutamate was significantly less than the increase from the 30-ng dose. The 90-ng (0.48 nmol) dose of L-glutamate kept animals awake for 2-3 h by eliminating both SWS and REM sleep. These results show that the L-glutamate microinjection into the PPT can increase wakefulness and/or REM sleep depending on the dosage. These findings support the hypothesis that excitation of the PPT cells is causal to the generation of wakefulness and REM sleep in the rat. In addition, the results of this study led to the identification of the PPT dosage of L-glutamate that optimally induces wakefulness and REM sleep. The knowledge of this optimal dose will be useful in future studies investigating the second messenger systems involved in the regulation of wakefulness and REM sleep.