The effect of propranolol on cAMP concentration in the rat preoptic region during the wake-sleep cycle

In control conditions preoptic cAMP concentration during wakefulness was significantly higher than during synchronized sleep. No differences in nucleotide concentration were observed in the cerebral cortex. Propranolol decreases brain cAMP concentration. This change was associated with the suppression of the difference observed between wakefulness and synchronized sleep in the preoptic region.     

Dynamic Mapping of the Temperature Fields of the Brain

The thermal fields and biopotentials of the brain were studied in 11 healthy subjects in the states of quiet wakefulness and sleep (stages I–IV). To this end, a new method of dynamic radiomapping was applied in parallel with the traditional method of EEG recording. The method of dynamic radiomapping is based on measuring the brain thermal radiation in the decimeter (40 cm) wave range. It allows the integral brain temperature to be recorded from deep inside and up to 2.5 cm from the surface with the help of 12 antennas applied to the skin. The temperature of the cerebral cortex of the human subject in the state of quiet wakefulness varied stochastically in the range of deviations of ±0.3°C in all areas. Changes in the brain functional state, i.e., the transition from wakefulness to sleep, were accompanied by either an increase in the variation range to ±0.5°C or the appearance of stationary foci of heating (by 0.9–1.3°C) or cooling (by –0.7°C) of individual locations and amplitudes.     

Memory for semantically related and unrelated declarative information: the benefit of sleep, the cost of wake

Numerous studies have examined sleep's influence on a range of hippocampus-dependent declarative memory tasks, from text learning to spatial navigation. In this study, we examined the impact of sleep, wake, and time-of-day influences on the processing of declarative information with strong semantic links (semantically related word pairs) and information requiring the formation of novel associations (unrelated word pairs). Participants encoded a set of related or unrelated word pairs at either 9 am or 9 pm, and were then tested after an interval of 30 min, 12 hr, or 24 hr. The time of day at which subjects were trained had no effect on training performance or initial memory of either word pair type. At 12 hr retest, memory overall was superior following a night of sleep compared to a day of wakefulness. However, this performance difference was a result of a pronounced deterioration in memory for unrelated word pairs across wake; there was no sleep-wake difference for related word pairs. At 24 hr retest, with all subjects having received both a full night of sleep and a full day of wakefulness, we found that memory was superior when sleep occurred shortly after learning rather than following a full day of wakefulness. Lastly, we present evidence that the rate of deterioration across wakefulness was significantly diminished when a night of sleep preceded the wake period compared to when no sleep preceded wake, suggesting that sleep served to stabilize the memories against the deleterious effects of subsequent wakefulness. Overall, our results demonstrate that 1) the impact of 12 hr of waking interference on memory retention is strongly determined by word-pair type, 2) sleep is most beneficial to memory 24 hr later if it occurs shortly after learning, and 3) sleep does in fact stabilize declarative memories, diminishing the negative impact of subsequent wakefulness.     

EEG study of the functional organization of the right and left hemisphere during solution of verbal and spatial problems

In adult healthy right-handed subjects, the expression and degree of synchronization of the EEG alpha-range rhythmic components in different areas of the right and left hemispheres, were studied in a state of quiet wakefulness and during solving of verbal and spatial tasks presented in the visual field. The EEG of quiet wakefulness was characterized by different distribution of the alpha-range rhythmic components in the right and left hemispheres; in the right hemisphere low frequencies (7.5-10.5 c/s) were more expressed and more coherent; in the left one--the high frequencies (10.5-13.5 c/s). The solving of tasks was accompanied--along with a decrease of the whole alpha-range power spectra both in the right and the left hemispheres--by a local increase of synchronization of certain components of this range; the increase was specific to the hemisphere and the kind of task. The increase of synchronization of low-frequency components was observed in the right hemisphere during solving of the spatial task and that of the high-frequency components was noticed in the left hemisphere during solving of the verbal task. On the basis of the data on hemispheric specificity of electric activity synchronization of the alpha-rhythm, a suggestion is made about a different character of the functional integration of the structures of the right and left hemispheres in the process of solving of spatial and verbal tasks.     

cGMP-Dependent Protein Kinase Type I Is Implicated in the Regulation of the Timing and Quality of Sleep and Wakefulness

Many effects of nitric oxide (NO) are mediated by the activation of guanylyl cyclases and subsequent production of the second messenger cyclic guanosine-3′,5′-monophosphate (cGMP). cGMP activates cGMP-dependent protein kinases (PRKGs), which can therefore be considered downstream effectors of NO signaling. Since NO is thought to be involved in the regulation of both sleep and circadian rhythms, we analyzed these two processes in mice deficient for cGMP-dependent protein kinase type I (PRKG1) in the brain. Prkg1 mutant mice showed a strikingly altered distribution of sleep and wakefulness over the 24 hours of a day as well as reductions in rapid-eye-movement sleep (REMS) duration and in non-REM sleep (NREMS) consolidation, and their ability to sustain waking episodes was compromised. Furthermore, they displayed a drastic decrease in electroencephalogram (EEG) power in the delta frequency range (1–4 Hz) under baseline conditions, which could be normalized after sleep deprivation. In line with the re-distribution of sleep and wakefulness, the analysis of wheel-running and drinking activity revealed more rest bouts during the activity phase and a higher percentage of daytime activity in mutant animals. No changes were observed in internal period length and phase-shifting properties of the circadian clock while chi-squared periodogram amplitude was significantly reduced, hinting at a less robust oscillator. These results indicate that PRKG1 might be involved in the stabilization and output strength of the circadian oscillator in mice. Moreover, PRKG1 deficiency results in an aberrant pattern, and consequently a reduced quality, of sleep and wakefulness, possibly due to a decreased wake-promoting output of the circadian system impinging upon sleep.     

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.     

Sleep deprivation induces the unfolded protein response in mouse cerebral cortex

Little is known about the molecular mechanisms underlying sleep. We show the induction of key regulatory proteins in a cellular protective pathway, the unfolded protein response (UPR), following 6 h of induced wakefulness. Using C57/B6 male mice maintained on a 12:12 light/dark cycle, we examined, in cerebral cortex, the effect of different durations of prolonged wakefulness (0, 3, 6, 9 and 12 h) from the beginning of the lights-on inactivity period, on the protein expression of BiP/GRP78, a chaperone and classical UPR marker. BiP/GRP78 expression is increased with increasing durations of sleep deprivation (6, 9 and 12 h). There is no change in BiP/GRP78 levels in handling control experiments carried out during the lights-off period. PERK, the transmembrane kinase responsible for attenuating protein synthesis, which is negatively regulated by binding to BiP/GRP78, is activated by dissociation from BiP/GRP78 and by autophosphorylation. There is phosphorylation of the elongation initiation factor 2alpha and alteration in ribosomal function. These changes are first observed after 6 h of induced wakefulness. Thus, prolonging wakefulness beyond a certain duration induces the UPR indicating a physiological limit to wakefulness.     

Variability of cortical evoked potentials to tooth pulp stimulation in unrestrained rats

In unrestrained adult rats evoked potentials were recorded by implanted electrodes in the somatosensory cortex in response to electrical stimulation of the pulp of an upper incisor. The spontaneous EEG, motor activity of the animal, and its respiratory movements were recorded simultaneously. Significant differences were observed in the configuration of the potentials and mean amplitude of the primary complex (P₁+N₁) during states of slow sleep, drowsiness, relaxed wakefulness, grooming, and investigative behavior; the amplitude of the primary complex during marked motor activity was reduced by more than an order of magnitude compared with that observed in a state of motor rest.In a state of relaxed wakefulness negative correlation was recorded between the amplitude of evoked potentials and momentary values of the respiration rate, weaker during periods of intensive motor activity. Meanwhile no direct parallel was observed between changes in potentials and respiration rate over the whole range of behavioral states studied: Depression of potentials was maximal during grooming whereas the respiration rate was maximal during investigative behavior.Paul Flechsig Institute for Brain Research, Karl Marx University, Leipzig, East Germany. Translated from Neirofiziologiya, Vol. 17, No. 1, pp. 27–35, January–February, 1985.     

The Effect of Old Age on the Free-Running Period of Circadian Rhythms in Rat

The free-running period is regarded to be an exclusive feature of the endogenous circadian clock. Changes during aging in the free-running period may therefore reflect age-related changes in the internal organization of this clock. However, the literature on alterations in the free-running period in aging is not unequivocal. In the present study, with various confounding factors kept to a minimum, it was found that the free-running periods for active wakefulness, body temperature, and drinking behavior were significantly shorter (by 12-17 min) in old than in young rats. In addition, it was found that the day-to-day stability of the different sleep states was reduced in old rats, whereas that of the drinking rhythm was enhanced. Transient cycles were not observed, nor were there any age-related differences in daily totals of the various sleep-wake states. The amplitudes of the circadian rhythms of active wakefulness, quiet sleep, and temperature were reduced, whereas those of paradoxical sleep and quiet wakefulness remained unchanged.     

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.     

The influence of prior wakefulness on REM sleep

Data from studies of naps and of shifted sleep were used to determine the relationship between two measures of rapid eye movement (REM) sleep (percentage of REM in the first 2 hr of sleep and REM latency) and prior wakefulness. For each sample, we calculated the difference between the observed value and that predicted by a cosine function that estimated the circadian rhythm of REM sleep propensity. The difference values were found to correlate reliably with hours and log hours of prior wakefulness. We conclude that while REM sleep is regulated in part by an endogenous circadian oscillator, it is also influenced by the duration of prior wakefulness.     

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.     

Midlatency auditory evoked responses: Differential effects of sleep in the cat

Middle latency responses (MLRs) in the 10–100 msec latency range, evoked by click stimuli, were studied in 8 adult cats during sleep-wakefulness to determine whether such changes in state were reflected by any MLR component. In particular, we wanted to determine whether the 20–22 msec positivity recorded at the vertex, ‘wave A,’ shown in previous studies to reflect a generator substrate within the ascending reticular formation, was tightly linked to changes in sleep-wakefulness, as reported for single neurons in the ascending reticular activating system. Evoked potentials were collected in 100 trial averages during continuous presentation of 1/sec clicks during initial awake recordings and thereafter during all-night sleep sessions. Continuously recorded EEG, EOG and EMG were scored for wakefulness, slow wave sleep (SWS), and rapid eye movement (REM) sleep during each evoked potential epoch. Recordings were obtained from electrodes implanted at the vertex and overlying the primary auditory cortex referenced to frontal sinus or to neck. In agreement with others, components of the auditory brain-stem response and the 12 msec primary cortical response showed no change in amplitude from wakefulness to either SWS or REM. Only wave A, among the components evaluated in the 1–100 msec range, decreased and disappeared during SWS and dramatically reappeared during REM to an amplitude equal to that during wakefulness. These data lend particular support to a functional relation between wave A and the ascending reticular activating system and suggest that this potential may provide a unique and dynamic probe of tonic brain activity. Moreover, this animal model provides a hypothetical basis for expecting a similar surface recorded potential in the human, a potential which has consequently been discovered.     

A corticotropin-releasing hormone antisense oligodeoxynucleotide reduces spontaneous waking in the rat

We have previously hypothesized that corticotropin-releasing hormone (CRH) is involved in the regulation of physiological waking. In this study, we tested the hypothesis that reduction of CRH peptide would reduce spontaneous wakefulness of rats. We administered intracerebroventricularly into rats at several circadian time points antisense or sense DNA oligodeoxynucleotides (ODNs) corresponding to the initiation codon of CRH mRNA and determined subsequent effects on wakefulness and sleep of the rat. Our results indicate that CRH antisense oligodeoxynucleotides reduce spontaneous wakefulness during the dark (active) period, but not during the light (rest) period of the light/dark cycle. The alterations in time spent awake are due to reduced wake bout numbers, rather than a change in wake bout duration. These reductions in wakefulness were mirrored by increases in slow-wave sleep, while rapid eye movement sleep was not affected. Corticosterone, used as an index of CRH in the hypothalamus, was reduced by CRH antisense oligodeoxynucleotides during the same time that spontaneous wakefulness was reduced, suggesting CRH peptide modulation as the mediator of this response. In contrast, CRH sense oligodeoxynucleotides did not alter any parameter of this study during either the dark or light period. These findings provide additional support for the hypothesis that CRH is involved in the regulation/modulation of wakefulness.     

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.     

The relevance of drowsiness in the circadian cycle of farm animals

Electrocorticography and concurrent electromyography were used to establish the quantitative duration of the states of sleep and wakefulness during the circadian cycle, and also during the night-time, in four species of farm animals. Associated attitudes and physiological data were also recorded. Drowsiness is described as a definite stable state of wakefulness, as opposed to alert wakefulness. The state of wakefulness occupied 85 per cent of the 24-hr period in the herbivorous species studied but only 67 per cent in pigs. Cows spend the greater proportion of this wakeful period in the state of drowsiness, horses spend the greater proportion in alert wakefulness. A considerable amount of the wakeful period of farm animals well-accustomed to their environment is spent in the drowsy state, when they are not asleep or actively ingesting or searching for food.     

Release of endogenous serotonin from "encéphale isolé" cats. II - Correlations with raphe neuronal activity and sleep and wakefulness

The discharge pattern of single neurons localized in raphe nuclei dorsalis and centralis superior was recorded in "encéphale isolé" cats, during sleep and wakefulness episodes occurring spontaneously or triggered by vago-aortic stimulation. In both nuclei, a similar and progressive decrease in frequency of discharges is generally observed during shifts between wakefulness, the transitional phase of sleep and paradoxical sleep. In addition, the release of serotonin (5-HT) has been studied with push-pull cannulae (caudate nucleus level) and superfusion techniques (cortical associative area) in relation to the different stages of consciousness. The results showed a clear diminution of endogenous 5-HT released during spontaneously occurring or vago-aortic triggered sleep.     

Changes in thermoregulation, sleep and the thyroid hormone concentration of the blood in the "critical" period of the entry into hibernation of the suslik Citellus parryi

During the first entering into hibernation in the ground squirrels there are periodic cessations of the process, especially during the transition to moderate and deep torpidity ("critical" periods) which significantly increase energy expenditure in animals during the phase of entering. During this period, high amplitude near-the-hour fluctuations are observed in total duration of wakefulness and sleep, contractile muscle activity, oxygen consumption, heart rate, brain temperature, and thyroid hormone concentration in the blood; at the end of this period, as well as during the exiting from it the duration of deep slow wave sleep significantly increases, paradoxical sleep is not identified. The data obtained confirm a hypothesis of "kindling" homeostasis as neuro-hormonal mechanism of the increase in thermal range of the activity of functional systems of the organism during the entering into torpidity in homoiothermic animals.     

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.     

Evolutionary aspects of sleep–wake cycle development in vertebrates (Modern state of the I.G. Karmanova’s sleep evolution theory)

The genetic basis of rest–activity circadian alternation in animal behavior is considered in the evolutionary range from bacteria to mammals. We scrutinize various concepts of sleep development in the animal world evolution as well as the I.G. Karmanova’s theory of the sleep–wake cycle evolution in vertebrates, beginning from wakefulness–primary sleep (or protosleep) in fish and amphibians through wakefulness–intermediate sleep in reptiles to wakefulness–slow wave sleep (SWS) and paradoxical sleep (PS) in birds and mammals. Primary sleep is represented by the three major sleep-like immobility states: catalepsy, catatonia and cataplexy. The main behavioral, somatovegetative and neurophysiological characteristics of primary sleep and the ancient activation pattern during primary sleep are described. The issues of which of these sleep manifestations are homologous to SWS, PS, hibernation and stress response are discussed. In conclusion, the general diagram of sleep evolution in vertebrates is presented, and the I.G. Karmanova’s contribution to evolutionary somnology is highlighted.