PACEMAKER PHASE CONTROL VERSUS MASKING BY LIGHT: SETTING THE CIRCADIAN CHRONOTYPE IN DUAL OCTODON DEGUS

There are two main processes involved in the expression of circadian rhythmicity: entrainment and masking. Whereas the first operates via the central pacemaker to anticipate predictable environmental conditions, masking (mainly induced by light) functions as a direct modulator of the circadian output signal induced by nonpredictable events. The Chilean rodent Octodon degus presents both diurnal and nocturnal chronotypes when given free access to an exercise wheel. Two steady-entrainment phases and graded masking by light seem to generate the wide variability of chronotypes in this species. The aim of this study was to characterize the differential masking by light according to the individual chronotypes, their stability over time, and the influence of wheel running availability and ambient temperature upon the degus' nocturnality. To this end, diurnal and nocturnal degus were subjected to ultradian cycles (1:1-h light-dark [LD]), with and without wheel running availability, and under both normal and high diurnal ambient temperature cycles. The present results show that diurnal and nocturnal degus present a stable masking by light, each according to its respective chronotype. Thus, whereas diurnal animals increased their activity with light, in nocturnal degus light induced a sharp drop in wheel running activity. These two types of masking responses appeared not only when the animals were synchronized to the 12:12-h LD cycle, but also under ultradian cycles. Different masking effects persisted when wheel running was made unavailable and when the animals shifted their circadian activity patterns in response to ultradian cycles or to diurnal exposure to high temperatures. In conclusion, our results show that the positive and negative masking effects of light on diurnal and nocturnal degus, respectively, seem to occur independently of relative phase control by the central pacemaker or the negative masking induced by high environmental temperatures. (Author correspondence: angerol@um.es)     

Multiple Component Analysis of Plasma Growth Hormone in Children with Standard and Short Stature

Growth hormone (GH) concentrations (in ng/ml) were determined by radioimmunoassay, in plasma obtained at about 3-hr intervals during a 24-hr sampling span, from 42 boys and 12 girls of short stature (2-4 standard deviations below their peer group mean), and 13 boys and 9 girls of standard stature. Subjects had 11.20 0.37 years of age at the time of study, and were living on a diurnal waking (∼07:30 to ∼22:30), nocturnal resting routine during sampling. Analysis of these data by single and population-mean cosinor methods as well as by analysis of variance revealed circadian and ultradian prominent components characterizing most groups. Accordingly, a multiple component analysis was undertaken for data of each group separately, as well as for all subjects. A comparison of circadian parameters indicates similar characteristics between short and standard children, whether one compares boys [P=0.674, 0.371 and 0.749 for comparison of rhythm adjusted means (M), amplitudes (A) and acrophases (), respectively], girls (P=0.993,0.914 and 0.397), or all children (P=0.859,0.712 and 0.865). Differences are found, however, in circasemidian characteristics as well as in the prominent 8-hr ultradian component documented for the short but not for the standard children. These ultradian components should be taken into consideration in the design and later evaluation of a time-specified treatment of children of short stature.     

A neural theory of circadian rhythms: split rhythms, after-effects and motivational interactions

A neural theory of the circadian pacemaker within the hypothalamic suprachiasmatic nuclei (SCN) is used to explain parametric data about mammalian operant behavior. The intensity, duration, and patterning of ultradian activity-rest cycles and the duration of circadian periods due to parametric (LL) and nonparametric (LD) lighting regimes are simulated. Paradoxical data about split rhythms and after-effects are explained using homeostatic and nonhomeostatic neural mechanisms that modulate pacemaker activity. These modulatory mechanisms enable the pacemaker to adjust to pervasive changes in its lighting regime, as during the passage of seasons, and to ultradian changes in internal metabolic conditions. The model circadian mechanisms are homologous to mechanisms that model hypothalamically mediated appetitive behaviors, such as eating. The theory thus suggests that both circadian and appetitive hypothalamic circuits are constructed from similar neural components. Mechanisms of transmitter habituation, opponent feedback interactions between on-cells and off-cells, homeostatic negative feedback, and conditioning are used in both the circadian and the appetitive circuits. Output from the SCN circadian pacemaker is assumed to modulate the sensitivity of the appetitive circuits to external and internal signals by controlling their level of arousal. Both underarousal and overarousal can cause abnormal behavioral syndromes whose properties have been found in clinical data. A model pacemaker can also be realized as an intracellular system.     

Ultradian oscillation in the heart rate of rainbow trout (Oncorhynchus mykiss)

• 1.1. Ultradian oscillations in the min and hr range on long-term (24-hr) computerized recordings of heart rate in rainbow trout Oncorhynchus mykiss, acclimated to 5, 10 and 15°C water temperature, were investigated. Eight-hour duration time series derived from the heart rate recordings were analysed for their harmonic content in the ultradian band by spectral analysis.
• 2.2. A significant ultradian rhythm at around 0.011 cycles/min (approximately 91-min period) was detected in the power spectral density functions of all the 8-hr duration time series derived from the heart rate recordings at the three experimental water temperatures.
• 3.3. The spectral power of the ultradian oscillation detected in heart rate of trout was found to increase significantly with increasing temperature.
• 4.4. The possible endogenous origin of the ultradian rhythm detected in heart rate of Oncorhynchus mykiss is discussed.

     

Principal components of electroencephalographic spectrum as markers of opponent processes underlying ultradian sleep cycles

Sleep-wake regulation involves reciprocal interactions between sleep- and wake-promoting processes that inhibit one another. To uncover the signatures of the opponent processes underlying ultradian sleep cycles, principal component analysis was performed on the sets of 16 single-Hz log-transformed electroencephalographic (EEG) power densities (1-16?Hz frequency range). Data were collected during unrestricted night sleep followed by 9 20-min naps (14 women aged 17-55 yrs) and during 12 20-min naps after either restriction or deprivation of sleep (9 males and 9 males, respectively, aged 18-22 yrs). It was found that any subset of power spectra could be reduced to the invariant four-principal component structure. The time courses of scores on these four components might be interpreted as the spectral EEG markers of the kinetics of two pairs of opponent chronoregulatory processes. In a sequence of ultradian sleep cycles, the 1st and 2nd components represent the alternations between competing drives for sleep and wakefulness, respectively, whereas the 3rd and 4th components reflect the alternations between light and deep sleep, respectively. The results suggest that principal component structuring of EEG spectrum can be employed for derivation of the parameters of the quantitative models conceptualizing the three major aspects of sleep-wake regulation—homeostatic, circadian, and ultradian processes.     

Ultradian and circadian compartmentalization of respiratory and metabolic exchanges in small laboratory vertebrates

Carbon dioxide emission (VCO2) taken as an index of respiratory and metabolic exchanges, was continuously recorded during 4-30 consecutive days in 100 quail, 87 chicks, 347 rats, 665 mice and 70 guinea-pigs which were under controlled environmental parameters. Harmonic analysis, fast Fourier transform, chi-square periodograms, peak and trough intervals were computed with VCO2 values obtained with CO2 concentrations sampled every 20 min on the CO2 recordings. In LD 12:12 alternation, circadian rhythms were observed in all quail, chicks, rats and mice, but only in 80% of the guinea-pigs. Ultradian VCO2 rhythms, with periods which show statistically significant interspecies differences, were assessed. For each of the 5 species these computed periods, which were the same in LL and DD, were: 1.17 h for quail and chickens, 1.25 h for rats, 1.50 h for mice and 1.0 h for guinea-pigs. In LD 12:12 these periods were different during L and D in quail, chicks, rats and mice, but not in guinea-pigs. The amplitudes of these ultradian variations were, according to the species, 10-20% of their mean VCO2 levels. These ultradian rhythms persist in the absence (or masking) of circadian rhythms, e.g. in LD 12:12 in 20% of guinea-pigs and in LL in 87% of Japanese quail and in 23% of Sprague-Dawley rats. Moreover, these ultradian rhythms persist during starvation, locomotor activity restraint and ageing. These ultradian VCO2 cycles which are related to rest-activity variations appear to be basic physiological rhythms with a genetic origin.     

Phase-Shifts of Apparent Orcadian Rhythms Due to West and East Transmeridian Flights or to Corresponding Night-Shift Sleep Displacements

Phase movements of apparent circadian rhythms during 2 wk of forward or backward displacement of the sleep-wake cycle were investigated in four experimental series in a subject. The 7-hr delay or advance of sleep due to a westward or an eastward transmeridian flight was duplicated by corresponding sleep displacements during experimental night shifts. Sudden phase advances (or delays) by several hours were observed in the rhythms of continuously recorded rectal temperature and urinary excretion rates (4-hr collection intervals) of adrenaline, noradrenaline and aldosterone the first day after sleep-wake displacement. The desired 7-hr phase-shifts were reached more quickly and completely when the phase was delayed than when it was advanced. In addition, the best-fitting period of these rhythms became shorter than 24 hr when the phase was delayed, and longer than 24 hr when it was advanced. The apparent rhythms of urine flow and electrolyte excretions (potassium, sodium, zinc) were much weaker and their phase movements more irregular than those of hormonal excretion. It is concluded that the sudden phase-shifts resulted from the immediate adaptation of the exogenous components of the rhythms to the demands of the displaced sleep-wake patterns (masking effects) and that the true phase-shifts of the endogenous components followed more slowly and gradually.     

Phase-shifts of apparent circadian rhythms due to west and east transmeridian flights or to corresponding night-shift sleep displacements

Phase movements of apparent circadian rhythms during 2 wk of forward or backward displacement of the sleep-wake cycle were investigated in four experimental series in a subject. The 7-hr delay or advance of sleep due to a westward or an eastward transmeridian flight was duplicated by corresponding sleep displacements during experimental night shifts. Sudden phase advances (or delays) by several hours were observed in the rhythms of continuously recorded rectal temperature and urinary excretion rates (4-hr collection intervals) of adrenaline, noradrenaline and aldosterone the first day after sleep-wake displacement. The desired 7-hr phase-shifts were reached more quickly and completely when the phase was delayed than when it was advanced. In addition, the best-fitting period of these rhythms became shorter than 24 hr when the phase was delayed, and longer than 24 hr when it was advanced. The apparent rhythms of urine flow and electrolyte excretions (potassium, sodium, zinc) were much weaker and their phase movements more irregular than those of hormonal excretion. It is concluded that the sudden phase-shifts resulted from the immediate adaptation of the exogenous components of the rhythms to the demands of the displaced sleep-wake patterns (masking effects) and that the true phase-shifts of the endogenous components followed more slowly and gradually.     

Ultradian Rhythms in Albino Rats during the Light Phase

The aim of this work is to investigate the ultradian rhythms of the rest-activity cycle of albino rats during the light phase. Occurrence (time-of-day) of 11 behavioral items was registered in a portable computer (HP95-LX). Each animal was visually and continuously observed for a interval of 2 hr, 3 hr after lights-on. Spectral analysis showed rest-activity cycles with statistically significant periods of 1 hr and also in the range of 10 to 20 min. As these rats were synchronized by a light-dark cycle (LD 12:12, 350:1 lux), these results suggest that ultradian rhythms are components of the circadian rest-activity cycle. The ultradian temporal organization of rest and activity behavioral items obtained by visual inspection is similar to the cycle of REM-NREM sleep stages obtained by EEG and described earlier in albino rats.     

Ultradian Rhythms in Albino Rats during the Light Phase

The aim of this work is to investigate the ultradian rhythms of the rest-activity cycle of albino rats during the light phase. Occurrence (time-of-day) of 11 behavioral items was registered in a portable computer (HP95-LX). Each animal was visually and continuously observed for a interval of 2 hr, 3 hr after lights-on. Spectral analysis showed rest-activity cycles with statistically significant periods of 1 hr and also in the range of 10 to 20 min. As these rats were synchronized by a light-dark cycle (LD 12:12, 350:1 lux), these results suggest that ultradian rhythms are components of the circadian rest-activity cycle. The ultradian temporal organization of rest and activity behavioral items obtained by visual inspection is similar to the cycle of REM-NREM sleep stages obtained by EEG and described earlier in albino rats.     

Lateralized ultradian rhythms of the right and left brain: temporal variations of tactile discrimination tested in German subjects.

Endogenous ultradian rhythms with a periodicity of 2-3 hours operate separately in the right and left hemispheres of the human brain and modulate physiological functions, perception and cognition. Since sensory pathways from either hand terminate in the contralateral hemisphere, ultradian rhythms of the right and left brain can be monitored by variations in the tactile discrimination of the left and right hand, respectively. Thirteen right-handed German males were tested every 15 minutes for 8 hours. Time series of the tactile error rate determined for the right and left hands oscillate with significantly different ultradian periodicities. Whereas cycles in tactile discrimination of the right hand (left hemisphere) have a periodicity of about 2 hours, tactile discrimination of the left hand (right hemisphere) is modulated by longer periods of about 3 hours. This is interpreted in terms of the overall functional asymmetry of the human brain. Since the left brain is the specialized locus for verbal processing and the right brain for visual-spatial processing, lateralized ultradian rhythms operating in the hemispheres may provide a distinct frame for long-term timing of neuronal processes underlying semantic and spatial mapping of the environment. This is particularly important for interpreting biosocial behavioural rhythms seen in humans living under natural conditions.     

Ultradian rhythmicity (circa 90 min) in physiologic processes ‐ evidence for multioscillatory phenomena

Abstract

Data accumulated in recent years have shown the existence of multiple about 90 min ultradian rhythms in gastric motility, urine flow and osmolality and physiologic indices of arousal. While these data support Kleitman's hypothesis that the REM‐NONREM sleep cycles are only fragments of a 24‐h rhythm (Basic Rest‐Activity Cycle) which is manifested in wakefulness in recurrent fluctuations in arousal, it further indicates that both the sleep and the waking rhythms are part of a more complex multioscillatory system with a dominant periodicity centered at 90 min.     

Principal Components of Electroencephalographic Spectrum as Markers of Opponent Processes Underlying Ultradian Sleep Cycles

Sleep-wake regulation involves reciprocal interactions between sleep- and wake-promoting processes that inhibit one another. To uncover the signatures of the opponent processes underlying ultradian sleep cycles, principal component analysis was performed on the sets of 16 single-Hz log-transformed electroencephalographic (EEG) power densities (1–16?Hz frequency range). Data were collected during unrestricted night sleep followed by 9 20-min naps (14 women aged 17–55 yrs) and during 12 20-min naps after either restriction or deprivation of sleep (9 males and 9 males, respectively, aged 18–22 yrs). It was found that any subset of power spectra could be reduced to the invariant four–principal component structure. The time courses of scores on these four components might be interpreted as the spectral EEG markers of the kinetics of two pairs of opponent chronoregulatory processes. In a sequence of ultradian sleep cycles, the 1st and 2nd components represent the alternations between competing drives for sleep and wakefulness, respectively, whereas the 3rd and 4th components reflect the alternations between light and deep sleep, respectively. The results suggest that principal component structuring of EEG spectrum can be employed for derivation of the parameters of the quantitative models conceptualizing the three major aspects of sleep-wake regulation—homeostatic, circadian, and ultradian processes. (Author correspondence: putilov@ngs.ru)     

Circadian and Ultradian Periodicities of Grooming Behavior in Family Groups of Common Marmosets (Callithrix jacchus) in Captivity

Three families' groups of common marmosets were observed to describe the characteristics of their grooming rhythmicity, as the duration of the episodes of self- and social grooming made and received by the animals, in captivity under natural environmental conditions. Data were collected by focal animal sampling, at 20 min hourly intervals during 16 non-consecutive days, from January to March in 1994 (sunrise: 05:24 h ± 2 min; sunset: 17:34 h ± 1 min). Time series were obtained for each individual and for each family through hourly duration of grooming. Family time serie was obtained through the mean of its individuals time series. Spectral analysis revealed statistically significant circadian rhythms for all families and individuals. Ultradian components were detected in 50% of the families and in 46.7% of the animals. Acrophases of self- and social grooming calculated by Single Cosinor took place between 9:21 h and 10:39 h, for the families. For individuals self- and social grooming made and received, acrophases occurred from 8:35 h to 12:43 h. The confidence limits of acrophases did not show differences between the families and the individuals within the families, irrespective of their sex, age and reproductive condition, suggesting that this behavior has a stronger temporal marking. Grooming has circadian and ultradian components of rhythmicity in captive families' groups of common marmosets, under natural environmental conditions. Since only some animals showed the ultradian component, it may be consequence of social or environmental masking, or yet phenotypic plasticity of temporal genotype. Further studies are needed to test these possibilities.     

Ultradian circa 112 hours rhythms: A multioscillatory system

Recent research has demonstrated rhythms in physiologic, behavioral, and endocrine processes with periodicity similar to that of the sleep REM-NONREM cycles. These findings confirm that part of Kleitman's Basic Rest-Activity (BRAC) hypothesis which predicted about $\text{1}\text{1}\text{2}\text{hour}$ cycles in waking levels of arousal. In contrast, however, with the BRAC model, which viewed the waking rhythms as fragments of the same oscillatory system controlling the REM-NONREM cycles, the accumulated data suggest that ultradian 90–100 min rhythms are generated by a multi-oscillatory system. It is hypothesized that the diverse ultradian variations in behavioral, physiologic and endocrine subsystems may play a role in the adaptation of group living animals to their environment.     

Masking in waved-2 mice: EGF receptor control of locomotion questioned

It has been suggested that epidermal growth factors (EGF) are responsible for the inhibition of locomotion by light (i.e., masking) in nocturnal rodents (Kramer et al., 2001). The poor masking response of waved-2 (Egfr^wa2) mutant mice, with reduced EGF receptor activity, was adduced in support of this idea. In the present work, we studied the responses to light over a large range in illumination levels, in a variety of tests, with pulses of light and with ultradian light-dark cycles in Egfr^wa2 mutant mice. No evidence suggested that normal functioning of epidermal growth factor receptors was required, or even involved, in masking.     

Enhanced antioxidant defense due to extracellular catalase activity in Syrian hamster during arousal from hibernation

Mammalian hibernators are considered a natural model for resistance to ischemia-reperfusion injuries, and protective mechanisms against oxidative stress evoked by repeated hibernation-arousal cycles in these animals are increasingly the focus of experimental investigation. Here we show that extracellular catalase activity provides protection against oxidative stress during arousal from hibernation in Syrian hamster. To examine the serum antioxidant defense system, we first assessed the hibernation-arousal state-dependent change in serum attenuation of cytotoxicity induced by hydrogen peroxide. Serum obtained from hamsters during arousal from hibernation at a rectal temperature of 32 degrees C, concomitant with the period of increased oxidative stress, attenuated the cytotoxicity four-fold more effectively than serum from cenothermic control hamsters. Serum catalase activity significantly increased during arousal, whereas glutathione peroxidase activity decreased by 50%, compared with cenothermic controls. The cytoprotective effect of purified catalase at the concentration found in serum was also confirmed in a hydrogen peroxide-induced cytotoxicity model. Moreover, inhibition of catalase by aminotriazole led to an 80% loss of serum hydrogen peroxide scavenging activity. These results suggest that extracellular catalase is effective for protecting hibernators from oxidative stress evoked by arousal from hibernation.     

Ultradian Mitotic Rhythms in Culture of Human Sarcomatous Bone Cells Originating from the Patient Before and After Chemotherapy

Bone sarcomatous cells derived from human malignant tumors were cultured. The mitotic index was recorded for 39 hr. When the cultured cells originated from patients with cancer disease before any chemotherapy, ultradian mitotic rhythms of a 6-9-hr period were detected, but in many cases only after a sensitive statistical analysis was performed. When the cultured cells originated from cancer patients undergoing chemotherapy, the mitotic index was decreased, and the amplitudes of the 6-9-hr component oscillations of the mitotic index were highly significantly increased. Damping and fading out of an ultradian mitotic rhythmicity was a bad prognostic portent in bone cancer. With reference to chemotherapy, the restored and amplified ultradian rhythmicity disclosed an appreciable antitumor effect and better survival prospects for the patient.     

Ultradian activity rhythms in large groups of newly hatched chicks (Gallus gallus domesticus)

A clutch of young chicks housed with a mother hen exhibit ultradian (within day) rhythms of activity corresponding to the brooding cycle of the hen. In the present study clear evidence was found of ultradian activity rhythms in newly hatched domestic chicks housed in groups larger than natural clutch size without a mother hen or any other obvious external time-keeper. No consistent synchrony was found between groups housed in different pens within the same room. The ultradian rhythms disappeared with time and little evidence of group rhythmicity remained by the third night. This disappearance over time suggests that the presence of a mother hen may be pivotal for the long-term maintenance of these rhythms. The ultradian rhythm of the chicks may also play an important role in the initiation of brooding cycles during the behavioural transition of the mother hen from incubation to brooding. Computer simulations of individual activity rhythms were found to reproduce the observations made on a group basis. This was achievable even when individual chick rhythms were modelled as independent of each other, thus no assumptions of social facilitation are necessary to obtain ultradian activity rhythms on a group level.     

Kidney proteome changes provide evidence for a dynamic metabolism and regional redistribution of plasma proteins during torpor-arousal cycles of hibernation

Hibernating ground squirrels maintain homeostasis despite extreme physiological challenges. In winter, these circannual hibernators fast for months while cycling between prolonged periods of low blood flow and body temperature, known as torpor, and short interbout arousals (IBA), where more typical mammalian parameters are rapidly restored. Here we examined the kidney proteome for changes that support the dramatically different physiological demands of the hibernator's year. We identified proteins in 150 two-dimensional gel spots that altered by at least 1.5-fold using liquid chromatography and tandem mass spectrometry. These data successfully classified individuals by physiological state and revealed three dynamic patterns of relative protein abundance that dominated the hibernating kidney: 1) a large group of proteins generally involved with capturing and storing energy were most abundant in summer; 2) a select subset of these also increased during each arousal from torpor; and 3) 14 spots increased in torpor and early arousal were enriched for plasma proteins that enter cells via the endocytic pathway. Immunohistochemistry identified α(2)-macroglobulin and albumin in kidney blood vessels during late torpor and early arousal; both exhibited regional heterogeneity consistent with highly localized control of blood flow in the glomeruli. Furthermore, albumin, but not α(2)-macroglobulin, was detected in the proximal tubules during torpor and early arousal but not in IBA or summer animals. Taken together, our findings indicate that normal glomerular filtration barriers remain intact throughout torpor-arousal cycles but endocytosis, and hence renal function, is compromised at low body temperature during torpor and then recovers with rewarming during arousal.