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The transfer of momentum from an animal to fluid in its wake is fundamental to many swimming and flying modes of locomotion. Hence, properties of the wake are commonly studied in experiments to infer the magnitude and direction of locomotive forces. The determination of which wake properties are necessary and sufficient to empirically deduce swimming and flying forces is currently made ad hoc. This paper systematically addresses the question of the minimum number of wake properties whose combination is sufficient to determine swimming and flying forces from wake measurements. In particular, it is confirmed that the spatial velocity distribution (i.e. the velocity field) in the wake is by itself insufficient to determine swimming and flying forces, and must be combined with the fluid pressure distribution. Importantly, it is also shown that the spatial distribution of rotation and shear (i.e. the vorticity field) in the wake is by itself insufficient to determine swimming and flying forces, and must be combined with a parameter that is analogous to the fluid pressure. The measurement of this parameter in the wake is shown to be identical to a calculation of the added-mass contribution from fluid surrounding vortices in the wake, and proceeds identically to a measurement of the added-mass traditionally associated with fluid surrounding solid bodies. It is demonstrated that the velocity/pressure perspective is equivalent to the vorticity/vortex-added-mass approach in the equations of motion. A model is developed to approximate the contribution of wake vortex added-mass to locomotive forces, given a combination of velocity and vorticity field measurements in the wake. A dimensionless parameter, the wake vortex ratio (denoted Wa), is introduced to predict the types of wake flows for which the contribution of forces due to wake vortex added-mass will become non-negligible. Previous wake analyses are re-examined in light of this parameter to infer the existence and importance of wake vortex added-mass in those cases. In the process, it is demonstrated that the commonly used time-averaged force estimates based on wake measurements are not sufficient to prove that an animal is generating the locomotive forces necessary to sustain flight or maintain neutral buoyancy.
The perifornical lateral hypothalamic area (PF-LHA) has been implicated in the control of several waking behaviours, including feeding, motor activity and arousal. Several cell types are located in the PF-LHA, including projection neurons that contain the hypocretin peptides (also known as orexins). Recent findings suggest that hypocretin neurons are involved in sleep-wake regulation. Loss of hypocretin neurons in the human disorder narcolepsy is associated with excessive somnolence, cataplexy and increased propensity for rapid eye movement (REM) sleep. However, the relationship of PF-LHA neuronal activity to different arousal states is unknown. We recorded neuronal activity in the PF-LHA of rats during natural sleep and waking. Neuronal discharge rates were calculated during active waking (waking accompanied by movement), quiet waking, non-REM sleep and REM sleep. Fifty-six of 106 neurons (53 %) were classified as wake/REM-related. These neurons exhibited peak discharge rates during waking and REM sleep and reduced discharge rates during non-REM sleep. Wake-related neurons (38 %) exhibited reduced discharge rates during both non-REM and REM sleep when compared to that during waking. Wake-related neurons exhibited significantly higher discharge rates during active waking than during quiet waking. The discharge of wake-related neurons was positively correlated with muscle activity across all sleep-waking states. Recording sites were located within the hypocretin-immunoreactive neuronal field of the PF-LHA. Although the neurotransmitter phenotype of recorded cells was not determined, the prevalence of neurons with wake-related discharge patterns is consistent with the hypothesis that the PF-LHA participates in the regulation of arousal, muscle activity and sleep-waking states.
The occurrence of high-frequency gamma activity (30-60 Hz) and its relationship to other frequency band activities were examined by spectral analysis of the electroencephalogram in association with sleep wake states and spontaneous behaviors in the rat. In the electroencephalogram, gamma wave activity was evident in unfiltered and high-frequency filtered recordings, in which it was prominent during attentive or active Wake episodes and during Paradoxical Sleep, when theta-like activity was also apparent. In amplitude spectra from these episodes, multiple peaks were evident within the gamma frequency band, indicating broad-band high-frequency activity, in association with a single low-frequency peak in the theta band. gamma peaks were attenuated during quiet Waking, in association with a low-frequency peak between theta and delta, and during Slow Wave Sleep, in association with a low-frequency peak in the delta band. In coherence spectra from ipsilateral cortical leads, peaks were also present within the gamma range and were significantly higher in Waking moving and Paradoxical Sleep than in Waking quiet and Slow Wave Sleep. In measures of frequency band amplitude, gamma activity (30.5-58.0 Hz) varied significantly across the sleep waking cycle, being similarly high during Wake and Paradoxical Sleep and lowest during Slow Wave Sleep. Across these states, gamma was negatively correlated with delta (1.5-4.0 Hz). In contrast, high beta (19.0-30.0 Hz) was significantly lower in Wake than in Slow Wave Sleep and was positively correlated with delta. gamma differed significantly across specific behaviors, being highest in Paradoxical Sleep with twitches and during Waking eating and moving behaviors, slightly lower in Waking attentive, lower in Waking grooming and as low in Waking quiet as during Slow Wave Sleep. These results indicate that the reciprocal variation of high-frequency gamma activity (and not beta) with low-frequency delta activity reflects the sleep waking cycle of the rat. Moreover, gamma activity reflects the degree of behavioral arousal, since it is high during active Waking, when the electromyogram is high, and low during quiet Waking, when the electromyogram is low. It also reflects cortical arousal, independent of motor activity, since it attains high levels in association with attentive immobility and maximal levels only during particular active behaviors (eating and moving and not grooming), and it also attains maximal levels during Paradoxical Sleep, when the nuchal electromyogram is minimal, but small twitches evidence dreaming. The co-variation of gamma and a slow oscillation in the theta band across states and behaviors suggests that a common system may modulate these fast and slow electroencephalogram rhythms, and that such modulation, potentially emanating from the basal forebrain, could predominate during certain states or behaviors, such as Paradoxical Sleep.
We examined the relationship between wake and sleep peritoneal temperature (T(ip)) during recovery from short-term (five rats, 5 days of deprivation) and long-term (nine rats, 14-21 days) total sleep deprivation (TSD). Mammalian body temperature normally declines in the passage from wakefulness to sleep. Recovery from TSD featured reductions of the typical wake-sleep T(ip) differences. Previous studies from our laboratory have shown that chronic TSD in the rat produces a progressive rise in energy production and an initial rise in wake T(ip), followed by a later fall in T(ip) to below baseline that becomes more acute as death becomes imminent. During recovery from both short-term TSD (wherein pre-recovery wake T(ip) was still above baseline) and long-term TSD (wherein pre-recovery wake T(ip) had fallen to below baseline), wake T(ip) and energy production quickly returned towards baseline. On the first recovery day, both short- and long-term TSD rats showed mean non-rapid eye movement (NREM) and paradoxical sleep (PS) T(ip) values that were slightly, although not significantly, above mean wake T(ip). In short-term TSD rats, wake-NREM and wake-PS T(ip) differences were reduced from baseline significantly (p < 0.0025) on the first recovery day and nonsignificantly on the remaining three recovery days. In long-term TSD rats, wake-NREM and wake-PS T(ip) differences were significantly (p < 0.001) reduced from baseline on the first four recovery day block. On the last four recovery day block, wake-sleep T(ip) differences tended to return toward baseline. Hypothalamic wake-sleep temperature differences in long-term TSD rats showed similar reductions during recovery. The reduction of wake-sleep temperature differences in recovery does not support either energy reduction or cooling functions for sleep.
Hypocretin/orexin modulates sleep-wake state via actions across multiple terminal fields. Within waking, hypocretin may also participate in high-arousal processes, including those associated with stress. The current studies examined the extent to which alterations in neuronal activity, as measured by Fos immunoreactivity, occur within both hypocretin-synthesizing and hypocretin-1 receptor-expressing neurons across varying behavioral state/environmental conditions associated with varying levels of waking and arousal. Double-label immunohistochemistry was used to visualize Fos and either prepro-hypocretin in the lateral hypothalamus or hypocretin-1 receptors in the locus coeruleus and select basal forebrain regions involved in the regulation of behavioral state/arousal. Animals were tested under the following conditions: 1). diurnal sleeping; 2). diurnal spontaneous waking; 3). nocturnal spontaneous waking; and 4). high-arousal waking (diurnal novelty-stress). Additionally, the effects of hypocretin-1 administration (0.07 and 0.7 nmol) on levels of Fos were examined within these two neuronal populations. Time spent awake, scored for the 90-min preceding perfusion, was largely comparable in diurnal spontaneous waking, nocturnal spontaneous waking and high-arousal waking. Nocturnal spontaneous waking and high-arousal waking, but not diurnal spontaneous waking, were associated with increased levels of Fos within hypocretin-synthesizing neurons, relative to diurnal sleeping. Within hypocretin-1 receptor-expressing neurons, only high-arousal waking was associated with increased levels of Fos. Hypocretin-1 administration dose-dependently increased levels of Fos within hypocretin-1 receptor-expressing neurons to levels comparable to, or exceeding, levels observed in high-arousal waking. Combined, these observations support the hypothesis that hypocretin neuronal activity varies across the circadian cycle. Additionally, these data suggest that waking per se may not be associated with increased hypocretin neurotransmission. In contrast, high-arousal states, including stress, appear to be associated with substantially higher rates of hypocretin neurotransmission. Finally, these studies provide further evidence indicating coordinated actions of hypocretin across a variety of arousal-related basal forebrain and brainstem regions in the behavioral state modulatory actions of this peptide system.
Sleep and wakefulness are governed by both the suprachiasmatic nuclei of the hypothalamus (SCN), and a sleep homeostatic process; however, the interaction of these control systems is not well understood. From rodent studies it has been assumed that the SCN promote neither wake nor sleep but gate the homeostatic sleep-promoting process. Yet in humans sleep tendency is lowest during the later waking hours of the day, and sleep duration can be predicted because of the precise circadian timing of waking. Thus in primates, the SCN could assure sleep-wake cycle consolidation by actively promoting or facilitating wakefulness. To evaluate this hypothesis, we examined the sleep-wake and sleep-stage patterns of intact and SCN-lesioned (SCNx) squirrel monkeys maintained in constant light. This diurnal primate has consolidated sleep and wake patterns more similar to man than rodents. Sleep-wake, sleep stages, brain temperature, and drinking circadian rhythms were eliminated, and total sleep time was significantly increased (4.0 hr, P < 0.01) in SCNx monkeys. However, total times in deeper stages of non-rapid eye movement (non-REM; e.g., delta sleep) and REM sleep were not significantly affected by SCN lesions. Increased total sleep time was associated with a reduction in subjective day wake consolidation, as evidenced by substantially shorter wake bout lengths in SCNx monkeys (15 +/- 6 min) as compared to intact monkeys (223 +/- 10 min; P < 0.0001, ANOVA). These findings show that the SCN influence the regulation of daily total wake and sleep times, and implicate an alternative sleep-wake regulatory model in which an SCN-dependent process actively facilitates the initiation and maintenance of wakefulness and opposes homeostatic sleep tendency during the subjective day in diurnal primates.
BACKGROUND: Several studies of healthy volunteers have revealed that subjective mood may vary with the duration of prior wakefulness and with the time of day. However, in these studies, the effects of extended wakefulness and circadian phase remained confounded, and the interaction of these 2 processes could not be assessed quantitatively. METHODS: In the present study, a total of 24 healthy young subjects (16 men, 8 women) lived on a 30-hour sleep-wake schedule for 19 to 23 days or on a 28-hour sleep-wake schedule for 33 to 36 days; both schedules induced desynchrony between the subjects' sleep-wake cycle and their endogenous circadian pacemaker. Subjective mood was assessed by 2 types of visual analog scales, which were administered twice every 2 hours and every 20 minutes, respectively, during all scheduled wakefulness episodes. A circadian phase and an interval elapsed since awakening were attributed to each data point, and circadian and wake-dependent fluctuations of mood were assessed. RESULTS: A significant variation of mood with circadian phase was observed, but no reliable main effect of the duration of prior wakefulness was found. A statistically significant interaction of circadian and wake-dependent fluctuations was evident; when the analysis was restricted to specific circadian phases, mood improved, deteriorated, or remained stable with the duration of prior wakefulness. CONCLUSIONS: These results indicate that, in healthy young subjects, subjective mood is influenced by a complex and nonadditive interaction of circadian phase and duration of prior wakefulness. The nature of this interaction is such that moderate changes in the timing of the sleep-wake cycle may have profound effects on subsequent mood.
Short sleep/dark durations, due to late bedtimes or early wake times or both, are common in modern society. We have previously shown that a series of days with a late bedtime phase delays the human dim light melatonin rhythm, as compared to a series of days with an early bedtime, despite a fixed wake time. Here we compared the effect of an early versus late wake time with a fixed bedtime on the human dim light melatonin rhythm. Fourteen healthy subjects experienced 2 weeks of short 6h nights with an early wake time fixed at their habitual weekday wake time and 2 weeks of long 9 h nights with a wake time that occurred 3h later than the early wake time, in counterbalanced order. We found that after 2 weeks with the late wake time, the dim light melatonin onset delayed by 2.4 h and the dim light melatonin offset delayed by 2.6 h (both p < 0.001), as compared to after 2 weeks with the early wake time. These results highlight the substantial influence that wake time, likely via the associated morning light exposure, has on the timing of the human circadian clock. Furthermore, the results suggest that when people truncate their sleep by waking early their circadian clocks phase advance and when people wake late their circadian clocks phase delay.
Neurons which discharge selectively during waking (waking selective) have been found in the tuberomamillary nucleus (TM) and adjacent areas of the posterior hypothalamus. Although they share some electrophysiological properties with aminergic neurons, there is no direct evidence that they are histaminergic. We have recorded from posterior hypothalamic neurons during the sleep-wake cycle in freely moving cats, and investigated the effects on waking selective neurons of specific ligands of histaminergic H3-receptors, which autoregulate the activity of histaminergic neurons. Two types of neurons were seen. Waking selective neurons, termed "waking-on (W-on)," were located exclusively within the TM and adjacent areas, and discharged at a low regular rate during waking (1.71-2.97 Hz), decreased firing during light slow wave sleep (SWS), became silent during deep SWS and paradoxical sleep (PS) and resumed their activity on, or a few seconds before, awakening. "Waking-related" neurons, located in an area dorsal to the TM, displayed a similar, although less regular, low rate of firing (1.74-5.41 Hz) and a similar discharge profile during the sleep-wake cycle; however, unlike "W-on" neurons, they did not completely stop firing during deep SWS and PS. Intramuscular (i.m.) injection of ciproxifan (an H3-receptor antagonist, 1mg/kg), significantly increased the discharge rate of W-on neurons and induced c-fos expression in histamine-immunoreactive neurons, whereas i.m. injection of imetit (an H3-receptor agonist, 1mg/kg) or microinjection of alpha-methylhistamine (another H3-receptor agonist, 0.025-0.1 microg/0.2 microl) in the vicinity of these cells significantly decreased their discharge rate. Moreover, the effect of the antagonist was reversed by the agonists and vice versa. In contrast, "waking-related" neurons were unaffected by these H3-receptor ligands. These data provide evidence for the histaminergic nature of "W-on" neurons and their role in cortical desynchronization during waking, and highlight the heterogeneity of posterior hypothalamic neuronal populations, which might serve different functions during the wakefulness.
The hypocretins (orexins) are a newly identified peptide family comprised of two peptides, hypocretin-1 and hypocretin-2. Recent observations suggest an involvement of these peptides in the regulation of behavioral state. For example, these peptides are found in a variety of brain regions associated with the regulation of forebrain neuronal and behavioral activity states. Furthermore, when infused into the lateral ventricles in awake animals, hypocretin-1 elicits increased duration of waking beyond that observed in vehicle-treated animals. Previous studies have been limited to an examination of the sleep-wake effects of hypocretin-1 in awake animals. Currently, the sleep-wake effects of hypocretin-2 and the extent to which hypocretins can initiate waking in the sleeping animal remain unclear. To better characterize the wake-promoting actions of the hypocretins, the current studies examined the sleep-wake effects of varying doses (0.007, 0.07 and 0.7 nmol) of hypocretin-1 and hypocretin-2 when administered into sleeping rats (e.g. remote-controlled infusions). Infusions of hypocretin-1 and hypocretin-2 into the lateral ventricles elicited a short latency (0.7 nmol hypocretin-1; 93+/-30 s from the start of the 120-s infusion) increase in electroencephalographic, electromyographic, and behavioral indices of waking. These infusions also produced substantial decreases in slow-wave and rapid-eye movement sleep. Hypocretin-1 was more potent than hypocretin-2 in these actions. Interestingly, hypocretin-1 infused into the fourth ventricle elicited less robust waking which occurred with a longer latency than infusions into the lateral ventricles. These latter observations suggest a forebrain site of action participates in hypocretin-1-induced waking. Within the forebrain, a variety of basal forebrain structures, including the medial preoptic area, the medial septal area and the substantia innominata, receive a moderate hypocretin innervation. Therefore, additional studies examined the sleep-wake effects of bilateral hypocretin-1 infusions into these basal forebrain structures. Robust increases in waking were observed following infusions into, but not outside, the medial septal area, the medial preoptic area and the substantia innominata. These results indicate a potentially prominent role of hypocretins in sleep-wake regulation via actions within certain basal forebrain structures and are consistent with studies indicating a prominent role of hypocretins in sleep/arousal disorders.