Changes in cyclic AMP concentration of the rat preoptic region as a result of long term exposure to cold

The cAMP concentration in the preoptic region was studied in rats during exposure to low ambient temperature (Ta: -10 degrees C) and after return to control Ta (22 degrees C). With respect to control cAMP concentration, changes were observed consisting of a decrease (delta cAMP: 4.19 /+- 0.15 pM/mg Pr; p < 0.001) at low Ta and an increase (delta cAMP: 1.40 /+- 0.13 pM/mg Pr; P < 0.05) after return to control Ta. In contrast, cortical cAMP concentration decreased both at low Ta (delta cAMP: 2.94 /+- 0.09 pM/mg Pr; P < 0.005) and after return to control Ta (delta cAMP: 3.21 /+- 0.09 pM/mg Pr; P < 0.001). such cAMP changes in the preoptic region may be related to different activation levels of thermoregulatory and sleep mechanisms.     

An EEG study of different behavioral states of freely moving dolphins]

ECoG and EMG of neck and eye muscles of four free moving dolphins were recorded during sleep-wakefulness cycle through chronically implanted electrodes. Wakefulness is accompanied by desynchronized ECoG, and slow sleep by synchronized ECoG, including the sleep spindles and theta- and delta-waves. The standard EMG criteria do not allow the discrimination between fast sleep and wakefulness in dolphins. Behavioral observations alone do not inform about dolphin's sleep or wakefulness. The respiration of dolphins may be observed during bilateral ECoG synchronization in slow sleep without arousal. ECoG synchronization as well as desynchronization may be observed when the contralateral eye is open.     

Ozone-induced paradoxical sleep decrease is related to diminished acetylcholine levels in the medial preoptic area in rats

Ozone (O3) produces significant effects on sleep, characterized specially by a decrease in paradoxical sleep (PS) and increase in slow-wave sleep (SWS), which in turn represent a sleep-wake cycle disruption. On the other hand, neuronal activity recorded in the cholinoceptive hypothalamic medial preoptic area (MPO) has been involved in the regulation of sleep. However, there is no direct evidence on the role that acetylcholine (Ach) release in the MPO plays in the sleep-wake cycle. In order to study this relation, we measured the Ach concentration in dialysates collected from MPO in rats exposed to coal-filtered air (clean air) for 48 h and in rats exposed to clean air for 24 h followed by 24-h of O3 exposure to 0.5 ppm. Polygraphic sleep records were taken simultaneously to neurochemical sampling. O3 was employed to disrupt the sleep-wake cycle and relate these changes with concomitant disruptions in Ach concentration dialyzed from MPO. A clear circadian pattern of Ach concentration was observed in dialysates from MPO and also in PS, SWS and wakefulness of rats exposed to filtered air. However, O3 exposure decreased the PS by 65% (Mann-Whitney's U-test, p相似文献   

Dynamics of neuronal activity in the lateral preoptic area of hypothalamus in the course of sleep-waking cycle

Frequency and patterns of activity of 106 neurons in the lateral preoptic area of unanesthetized cats were studied under conditions of indolent head fixation. It was shown that this structure contains two somnogenic neuronal populations with different functions. Neurons increasing their discharge frequency during transition from active to quiet wakefulness and subsequent sleep development to the point of phasic stage of paradoxical sleep development are considered as elements of an anti-waking system, which is involved in the mechanisms of sleep onset and deepening by means of inactivation of the arousal system. Neurons displaying the highest firing rates during light slow-wave sleep and synchronization of discharges with sleep spindles are considered as elements of a slow-wave sleep network.     

Role of cholinergic mechanisms of the ventrolateral preoptico-anterior hypothalamic area in regulation of sleep and wakefulness states in pigeons

Maintenance of wakefulness is established to accomplish muscarinic (M-) cholinergic receptor activation in the ventrolateral preoptic area of the hypothalamus. The "muscarinic" wakefulness is characterized by enhancement of electroencephalogram (EEG) power spectra in the 0.75-12 Hz band and by increase in brain temperature. Activation of nicotinic (N-) cholinergic receptors of the area produces an increase in the duration of slow wave sleep, EEG power spectra reduction in the 0.75-7 Hz band, a decrease in brain temperature. And its hyperactivation leads to wakefulness, during its episodes the brain temperature decreases. During M- and N-cholinergic receptor blockade, the sleep-wakefulness and thermoregulation changes opposite to their activation were found. It is suggested that M- and N-cholinergic receptors of the ventrolateral preoptic area in pigeons participate in the sleep-wakefulness regulation and this effect is related to influence of this area on GABA-ergic system.     

Involvement of Autonomic Nervous Activity Changes in Gastroesophageal Reflux in Neonates during Sleep and Wakefulness

Background

It has been suggested that disturbed activity of the autonomic nervous system is one of the factors involved in gastroesophageal reflux (GER) in adults. We sought to establish whether transient ANS dysfunction (as assessed by heart rate variability) is associated with the occurrence of GER events in neonates during sleep and wakefulness.

Methods

Nineteen neonates with suspected GER underwent simultaneous, synchronized 12-hour polysomnography and esophageal multichannel impedance-pH monitoring. We compared changes in HRV parameters during three types of periods (control and prior to and during reflux) with respect to the vigilance state.

Results

The vigilance state influenced the distribution of GER events (P<0.001), with 53.4% observed during wakefulness, 37.6% observed during active sleep and only 9% observed during quiet sleep. A significant increase in the sympathovagal ratio (+32%, P=0.013) was observed in the period immediately prior to reflux (due to a 15% reduction in parasympathetic activity (P=0.017)), relative to the control period. This phenomenon was observed during both wakefulness and active sleep.

Conclusion

Our results showed that GER events were preceded by a vigilance-state-independent decrease in parasympathetic tone. This suggests that a pre-reflux change in ANS activity is one of the factors contributing to the mechanism of reflux in neonates.     

Ozone exposure alters 5-hydroxy-indole-acetic acid contents in dialysates from dorsal raphe and medial preoptic area in freely moving rats. Relationships with simultaneous sleep disturbances

Ozone (O3) has been reported to affect sleep patterns and also striatal and mesencephalic contents of 5-hydroxy-indole-acetic acid (5-HIAA) in rats. The aim of this work was to elucidate the effects of O3 exposure in rats upon extracellular 5-HIAA levels in the dorsal raphe (DR) and the hypothalamic medial preoptic area (MPO), two structures involved in sleep-wake homeostasis. Exposure to O3 followed a bell-shaped diurnal pattern, similar to that observed in cities with high air pollution levels. The highest O3 concentration employed was 0.5 ppm. Simultaneous polygraphic records were performed to evaluate the concomitant effects of this exposure model on sleep patterns. Results showed that extracellular 5-HIAA levels increased by 28% in the DR (P=0.0213) while paradoxical sleep (PS) decreased by 56% (P=0.0000) during the light O3 exposure phase. A decrease of 32% in 5-HIAA levels in the MPO (P=0.0450), and of 22% in slow wave sleep (SWS) (P=0.0002) and an increase of 21% in wakefulness (P=0.0430) during the dark post-exposure (Dpost) phase were also observed. We propose that the decrease in PS is the behavioral expression of disruptions of serotonergic DR modulation and, that post-exposure effects observed in the MPO can be explained on the basis of the hypothalamic role in the sleep-wake cycle.     

Compensatory sleep response to 12 h wakefulness in young and old rats

There is a pronounced decline in sleep with age. Diminished output from the circadian oscillator, the suprachiasmatic nucleus, might play a role, because there is a decrease in the amplitude of the day-night sleep rhythm in the elderly. However, sleep is also regulated by homeostatic mechanisms that build sleep drive during wakefulness, and a decline in these mechanisms could also decrease sleep. Because this question has never been addressed in old animals, the present study examined the effects of 12 h wakefulness on compensatory sleep response in young (3.5 mo) and old (21.5 mo) Sprague-Dawley and F344 rats. Old rats in both strains had a diminished compensatory increase in slow-wave sleep (SWS) after 12 h of wakefulness (0700-1900, light-on period) compared with the young rats. In contrast, compensatory REM sleep rebound was unaffected by age. To assess whether the reduced SWS rebound in old rats might result from loss of neurons implicated in sleep generation, we counted the number of c-Fos immunoreactive (c-Fos-ir) cells in the ventral lateral preoptic (VLPO) area and found no differences between young and old rats. These findings indicate that old rats, similar to elderly humans, demonstrate less sleep after prolonged wakefulness. The findings also indicate that although old rats have a decline in sleep, this cannot be attributed to loss of VLPO neurons implicated in sleep.     

Electrical responses of olfactory structures and amygdala of dogs in the paradoxical phase of sleep

Electrical activity of the olfactory bulb, olfactory tubercle, amygdala, hippocampus, hypothalamus, and neocortex in the various phases of natural sleep was studied in chronic experiments on dogs under conditions close to those of free behavior. During paradoxical sleep it was found that a high-frequency synchronized rhythm of sinusoidal waves with a frequency of 36–42 Hz arises in the olfactory structures and amygdala. Generation of this activity during paradoxical sleep, by contrast with wakefulness, was unconnected with stimulation of the olfactory receptors and was probably purely central in origin. A study of the dynamics of the olfacto-amygdaloid rhythm during the paradoxical phase, and its comparison with somatic, autonomic, and EEG correlates of sleep, led to the conclusion that this rhythm is a specific EEG correlate of the paradoxical phase of sleep in dogs.     

Dynamics of neuronal activity in the posterior hypothalamus during alternating phases of the sleep-wake cycle

The dynamics of neuronal activity in the posterior hypothalamus in different phases of the sleep-wake cycle were investigated during experiments on free-ranging cats. The highest frequency discharges were found to occur in 89.3% of neurons belonging to this region during the stages of active wakefulness and emotionally influenced paradoxical sleep. These neurons become less active during restful wakefulness and the unemotional stage of paradoxical sleep; this reduced activity can be most clearly observed in the context of slow-wave sleep. It was found that 7.1% of test neurons discharged at the highest rate during the stage of active wakefulness. They did not achieve an activity level characteristic of active wakefulness during the period of paradoxical sleep, although activity level was higher than during other states. Only 3.6% of neurons followed the opposite pattern, with discharges succeeding more frequently in slow-wave sleep and activity reduced to an equal degree during wakefulness and paradoxical sleep. The neurophysiological mechanisms governing the sleep-wake cycle and how the posterior hypothalamus contributes to these mechanisms are discussed.I. S. Beritashvili Institute of Physiology, Academy of Sciences of Georgian SSR, Tbilisi. Translated from Neirofiziologiya, Vol. 20, No. 2, pp. 160–167, March–April, 1988.     

Key roles of the histaminergic system in sleep-wake regulation

Histamine plays an important role in mediating wakefulness in mammals. Based on the findings from gene-manipulated mice, we provide several lines of evidence showing the roles of the histaminergic system in the somnogenic effects of prostaglandin (PG) D2 and adenosine, and in the arousal effects of PGE2 and orexin. PGD2 activates DP1 receptors (R) to promote sleep by stimulating them to release adenosine. The released adenosine activates adenosine A2AR and subsequently excites the ventrolateral preoptic area (VLPO), one of the sleep centers in the anterior hypothalamus. VLPO neurons then send inhibitory signals to downregulate the histaminergic tuberomammillary nucleus (TMN), which contributes to arousal. A1R is expressed in histaminergic neurons of the rat TMN. Adenosine in the TMN inhibits the histaminergic system via A1R and promotes non–rapid eye movement sleep. Conversely, both endogenous PGE2 and orexin activate the histaminergic system through EP4R and OX-2R, respectively, to promote wakefulness via histamine H1R. Furthermore, the arousal effect of ciproxifan, H3R antagonist, depends on the activation of histaminergic systems. These findings indicate that VLPO and TMN regulate sleep and wakefulness by means of a “flip-flop” mechanism operating in an anti-coincident manner during sleep–wake state transitions.

     

Microdialysis perfusion of orexin-A in the basal forebrain increases wakefulness in freely behaving rats

Recent work indicates that the orexin/hypocretin-containing neurons of the lateral hypothalamus are involved in control of REM sleep phenomena, but site-specific actions in control of wakefulness have been less studied. Orexin-containing neurons project to both brainstem and forebrain regions that are known to regulate sleep and wakefulness, including the field of cholinergic neurons in the basal forebrain (BF) that is implicated in regulation of wakefulness, and includes, in the rat, the horizontal limb of the diagonal band, the substantia innominata, and the magnocellular preoptic region. The present study used microdialysis perfusion of orexin-A directly in the cholinergic BF region of rat to test the hypothesis that orexin-A enhances W via a local action in the BF. A significant dose-dependent increase in W was produced by the perfusion of three doses of orexin-A in the BF (0.1, 1.0, and 10.0 microM), with 10.0 microM producing more than a 5-fold increase in wakefulness, which occupied 44% of the light (inactive) phase recording period. Orexin-A perfusion also produced a significant dose-dependent decrease in nonREM sleep, and a trend-level decrease in REM sleep. The results clearly demonstrate a potent capacity of orexin-A to induce wakefulness via a local action in the BF, and are consistent with previous work indicating that the BF cholinergic zone neurons have a critical role in the regulation of EEG activation and W. The data suggest further that orexin-A has a significant role in the regulation of arousal/wakefulness, in addition to the previously described role of orexin in the regulation and expression of REM sleep and REM sleep-related phenomena.     

Sleep and wakefulness in the green iguanid lizard (Iguana iguana)

The reptile Iguana iguana exhibits four states of vigilance: active wakefulness (AW), quiet wakefulness (QW), quiet sleep (QS) and active sleep (AS). Cerebral activity decreases in amplitude and frequency when passing from wakefulness to QS. Both parameters show a slight increase during AS. Heart rate is at a maximum during AW (43.8+/-7.9 beats/min), decreases to a minimum in QS (25.3+/-3.2 beats/min) and increases in AS (36.1+/-5.7 beats/min). Tonical and phasical muscular activity is present in wakefulness, decreases or disappears in QS and reappears in AS. Single or conjugate ocular movements are observed during wakefulness, then disappear in QS and abruptly reappear in AS. Although these reptiles are polyphasic, their sleep shows a tendency to concentrate between 20:00 and 8:00 h. Quiet sleep occupies the greater percentage of the total sleep time. Active sleep episodes are of very short duration, showing an average of 21.5+/-4.9 (mean+/-SD). Compensatory increment of sleep following its total deprivation was significant only for QS. Reaction to stimuli decreased significantly when passing from wakefulness to sleep. It is suggested that the lizard I. iguana displays two sleep phases behaviorally and somatovegetatively similar to slow wave sleep and paradoxical sleep in birds and mammals.     

Participation of muscarinic and nicotinic cholinoreceptors of hypothalamic preoptic area in control of thermoregulation and of wakefulness and sleep states in the pigeons <Emphasis Type="Italic">Columba livia</Emphasis>

By using electrophysiological methods, it has been established that muscarinic (M-) cholinergic mechanisms of the ventrolateral preoptic area (VLPA) of pigeon hypothalamus participate in maintenance of wakefulness, whereas nicotinic (N-) mechanisms—in maintenance of the nonrapid-eye movement sleep (slow sleep). Activation of the VLPA M-cholinergic receptors has been found to be accompanied by an elevation of the brain temperature, by development of peripheral vasoconstriction, and by an increase in the muscle contractive activity. Activation of N-cholinoreceptors leads to a decrease in the brain temperature and development of peripheral vasoconstriction. It is suggested that the VLPA M-and N-cholinergic receptors are involved in different mechanisms of regulation of wakefulness and sleep states and brain temperature in pigeons.     

Temporal patterns of unit activity of mesencephalic reticular nuclei during sleep and waking

Temporal patterns of unit activity in the mesencephalic reticular nuclei (n. cuneiformis, n. parabrachialis) were studied in unrestrained rats during the sleep-waking cycle; activity was derived by means of movable metallic microelectrodes. Analysis of the data showed that most neurons of these mesencephalic reticular nuclei (76 and 66% respectively) generate activity with the highest frequency during active waking and the emotional stage of paradoxical sleep; they discharge with lower frequency during passive wakefulness and the nonemotional stage of paradoxical sleep, and they exhibit least activity during slow-wave sleep. Comparatively few neurons (24 and 15%) demonstrate the opposite kind of temporal pattern of activity: They discharge more intensively during slow-wave sleep and more slowly during active wakefulness and the emotional stage of paradoxical sleep. Activity of these neurons during quiet wakefulness and the nonemotional stage of paradoxical sleep reaches the level of activity observed during slow-wave sleep. Neurons discharging intensively during active wakefulness were found in n. parabrachialis; their discharge frequency during passive wakefulness and slow-wave sleep and its frequency was least during paradoxical sleep. The similarity and differences of the neurophysiological mechanisms of regulation of the phases and stages of the sleepwaking cycle are discussed.I. S. Beritashvili Institute of Physiology, Academy of Sciences of the Georgian SSR, Tbilisi. Translated from Neirofiziologiya, Vol. 16, No. 5, pp. 678–690, September–October, 1984.     

Participation of GABAergic Mechanisms of Hypothalamus Ventrolateral Preoptic Area in Regulation of Sleep and Wakefulness and Temperature Homeostasis in the Pigeon <Emphasis Type="Italic">Columba livia</Emphasis>

A comparative analysis of awakening, somnogenic, and thermoregulating effects of agonists and antagonists of GABAA,B-receptors after microinjections to neuronal populations of ventrolateral preoptic area (VLPA) of hypothalamus was carried out for the first time in representatives of the avian class (pigeon). It has bee established that: (1) VLPA of hypothalamus contains populations of neurons differing by their function and representation of receptor types and participating in control of wakefulness, sleep, and thermoregulation; (2) executive GABA_A-ergic mechanisms of maintenance of the slow-wave sleep (SWS) are located predominantly in the caudal part of the hypothalamic VLPA; (3) GABA_A,B-ergic mechanisms of control of thermal homeostasis are located predominantly in the caudal part of VLPA. It is suggested that the maintenance of SWS depends on an increase of activity of inhibitory GABAergic VLPA mechanisms leading to inactivation of neuronal networks of wakefulness outside VLPA and on a reduction of activity of the stimulatory aminergic systems present in the preoptic area and outside it.     

Sleep Deprivation Reveals Altered Brain Perfusion Patterns in Somnambulism

Background

Despite its high prevalence, relatively little is known about the pathophysiology of somnambulism. Increasing evidence indicates that somnambulism is associated with functional abnormalities during wakefulness and that sleep deprivation constitutes an important drive that facilitates sleepwalking in predisposed patients. Here, we studied the neural mechanisms associated with somnambulism using Single Photon Emission Computed Tomography (SPECT) with ^99mTc-Ethylene Cysteinate Dimer (ECD), during wakefulness and after sleep deprivation.

Methods

Ten adult sleepwalkers and twelve controls with normal sleep were scanned using ^99mTc-ECD SPECT in morning wakefulness after a full night of sleep. Eight of the sleepwalkers and nine of the controls were also scanned during wakefulness after a night of total sleep deprivation. Between-group comparisons of regional cerebral blood flow (rCBF) were performed to characterize brain activity patterns during wakefulness in sleepwalkers.

Results

During wakefulness following a night of total sleep deprivation, rCBF was decreased bilaterally in the inferior temporal gyrus in sleepwalkers compared to controls.

Conclusions

Functional neural abnormalities can be observed during wakefulness in somnambulism, particularly after sleep deprivation and in the inferior temporal cortex. Sleep deprivation thus not only facilitates the occurrence of sleepwalking episodes, but also uncovers patterns of neural dysfunction that characterize sleepwalkers during wakefulness.     

Collapsibility of the human upper airway during normal sleep

Upper airway resistance (UAR) increases in normal subjects during the transition from wakefulness to sleep. To examine the influence of sleep on upper airway collapsibility, inspiratory UAR (epiglottis to nares) and genioglossus electromyogram (EMG) were measured in six healthy men before and during inspiratory resistive loading. UAR increased significantly (P less than 0.05) from wakefulness to non-rapid-eye-movement (NREM) sleep [3.1 +/- 0.4 to 11.7 +/- 3.5 (SE) cmH2O.1-1.s]. Resistive load application during wakefulness produced small increments in UAR. However, during NREM sleep, UAR increased dramatically with loading in four subjects although two subjects demonstrated little change. This increment in UAR from wakefulness to sleep correlated closely with the rise in UAR during loading while asleep (e.g., load 12: r = 0.90, P less than 0.05), indicating consistent upper airway behavior during sleep. On the other hand, no measurement of upper airway behavior during wakefulness was predictive of events during sleep. Although the influence of sleep on the EMG was difficult to assess, peak inspiratory genioglossus EMG clearly increased (P less than 0.05) after load application during NREM sleep. Finally, minute ventilation fell significantly from wakefulness values during NREM sleep, with the largest decrement in sleeping minute ventilation occurring in those subjects having the greatest awake-to-sleep increment in UAR (r = -0.88, P less than 0.05). We conclude that there is marked variability among normal men in upper airway collapsibility during sleep.     

Sleep contributes to dendritic spine formation and elimination in the developing mouse somatosensory cortex

Sleep is maximal during early postnatal life when rapid and extensive synapse remodeling occurs. It remains unknown whether and how sleep affects synapse development and plasticity. Using transcranial two‐photon microscopy, we examined the formation and elimination of fluorescently labeled dendritic spines and filopodia of Layer 5 pyramidal neurons in the barrel cortex of 3‐week‐old mice during wakefulness and sleep. We observed high turnover of dendritic protrusions over 2 h in both wake and sleep states. The formation rate of dendritic spines or filopodia over 2 h was comparable between the two states. The elimination rate of dendritic spines or filopodia was lower during 2‐h wakefulness than during 2‐h sleep. Similar results were observed on dendritic protrusion dynamics over 12‐h light/dark cycle when mice spent more time asleep or awake. The substantial remodeling of dendritic protrusions during the sleep state supports the notion that sleep plays an important role in the development and plasticity of synaptic connections in the mouse cortex. © 2011 Wiley Periodicals, Inc. Develop Neurobiol, 2012     

Arytenoideus muscle activity in normal adult humans during wakefulness and sleep

The respiratory-related activity of the arytenoideus (AR) muscle, a vocal cord adductor, was investigated in 10 healthy adults during wakefulness and sleep. AR activity was measured with intramuscular hooked-wire electrodes implanted by means of a fiber-optic nasopharyngoscope. Correct placement of the electrodes was confirmed by discharge patterns during voluntary maneuvers. The AR usually exhibited respiratory-related activity during quiet breathing in all awake subjects. Tonic activity was frequently present throughout the respiratory cycle. The pattern of phasic discharge during wakefulness exhibited considerable intrasubject variability both in timing and level of activity. Phasic activity usually began in midinspiration and terminated in mid- to late expiration. Periods of biphasic discharge were observed in four subjects. Phasic discharge primarily confined to expiration was also commonly observed. During quiet breathing in wakefulness, the level of phasic AR activity appeared to be directly related to the time of expiration. The AR was electrically silent in the six subjects who achieved stable periods of non-rapid-eye-movement sleep. Rapid-eye-movement sleep was observed in three subjects and was associated with sporadic paroxysmal bursts of AR activity. The results during wakefulness indicate that vocal cord adduction in expiration is an active phenomenon and suggest that the larynx may have an active role in braking exhalation.