Light entrainment of the mammalian biological clock.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
W J Rietveld
Publications and source records attributed to W J Rietveld.
General introduction to chronobiology.
Rhythmicity is part of our life. All living organisms exhibit in some way or another a form of rhythmicity. Some of these rhythms have a geophysical counterpart in the environment. These are the so-called biological rhythms. This paper gives an introduction to the circadian rhythms, i.e., those rhythms with a period length of about one day. General characteristics and properties are described as well as the control and disturbances of these rhythms.
Chronobiology Phenomena↗
Ionic currents in cultured rat suprachiasmatic neurons.
Whole-cell voltage-clamp recordings were made from cultured neurons obtained by dissociation of the suprachiasmatic area of rat fetuses. Neurons were held for seven to 14 days in culture. These neurons possessed several voltage-dependent ionic currents. A transient inward Na+ current was present, which could be completely blocked by tetrodotoxin. No inward Ca2+ currents were detected. Three types of outward K+ currents were recorded, which could be separated to a reasonable extent by their differences in voltage sensitivity and pharmacology. These K+ currents corresponded to the transient current IA, the delayed rectifier current IKo and a calcium-dependent current IK(Ca) as described in other neurons. The A current activated at -50 mV, reached half-maximal conductance at about -30 mV and maximum conductance between 0 and 30 mV. During depolarizing steps it inactivated completely within 100 ms and steady-state inactivation was half-maximal at -66 mV. The outward rectifier activated at -30 mV, reached half-maximal conductance close to 0 mV and maximum conductance at about 70 mV. Slow inactivation of IKo occurred with 50% reduction in amplitude at the end of 2 s depolarizations above 0 mV. The K+ channel blocker 4-amino-pyridine (4 mM) reduced the amplitude of IA by 21% and of IKo by 32%, whereas tetraethylammonium (10 mM) decreased IA by 27% and IKo by 83%. The calcium-dependent K+ component was also voltage dependent and was present at voltages more positive than 0 mV. No inward rectifying K+ current was present. Considering its voltage dependence, IA must play a role in determining the excitability of these neurons, through its probable influence on the action potential threshold and interspike interval. Both IA and IKo should take part in membrane repolarization following an action potential. The Ca(2+)-dependent current should also contribute to repolarization following any event which gives rise to an increase in intracellular Ca2+. Apart from IA, which may make a slight contribution, none of these currents appear to be involved in determining the resting membrane potential. All three outward current components will act together in suprachiasmatic neurons to control their spontaneous firing frequency, which is the major feature of the output of these neurons in vivo. Variations in properties of these conductances could contribute to the circadian rhythm in firing frequency described in suprachiasmatic hypothalamic neurons.
4-Aminopyridine↗
Suprachiasmatic lesions eliminate 24-h blood pressure variability in rats.
To evaluate whether the suprachiasmatic nuclei (SCN) control 24-h rhythmicity in cardiovascular function, rats were subjected to computerized recording of 24-h blood pressure (BP) and heart rate (HR) following SCN lesions. In sham- and nonlesioned rats, circadian patterns of BP and HR ran in phase with those in feeding behavior. In SCN-lesioned rats circadian rhythmicity in BP, HR and food intake were abolished. Minute-to-minute variation of BP and HR was similar as in sham- and nonlesioned rats. We conclude that long-term but not short-term variability of blood pressure and heart rate is largely determined by SCN-controlled activity levels.
Animals↗
Proliferation profile of benign and premalignant cervical epithelium as established by PCNA staining pattern.
Since immunohistochemical detection of proliferating cell nuclear antigen (PCNA) is closely related to the cell cycle, this method can be used to visualize proliferative activity in paraffin sections of benign and premalignant cervical lesions. This was done in two types of benign lesions, immature and mature metaplasia, and the three types of CIN (I, II, and III). PCNA staining was assessed as heavy, faint, or negative nuclei in the deep, middle, and superficial layers of the epithelium. In the analysis of variance, significant differences between the three layers and between the five groups were found. The PCNA values can be helpful to distinguish immature metaplasia from CIN I. The values for PCNA-positive (heavy+faint) for an individual lesion at the three layers constitute its proliferation profile. The PCNA profiles of the CIN lesions differ fundamentally from the metaplasia profiles. It is conceivable that for an individual CIN lesion, PCNA staining might be prognostically more valuable than its CIN grade.
Cell Division↗
Functional development of fetal suprachiasmatic nucleus grafts in suprachiasmatic nucleus-lesioned rats.
Recovery of circadian drinking rhythms in suprachiasmatic nucleus (SCN)-lesioned rats after fetal SCN grafting was related to the immunocytochemical appearance and fiber outgrowth of vasopressin (VP)-, vasoactive intestinal polypeptide (VIP)-, and somatostatin (SOM)-containing neurons in the implants. At 4 weeks postgrafting, the first recovered animal was found. After longer survival times, 38% of the animals showed recovery. Immunocytochemical evaluation indicated that full maturation of the SCN grafts was not reached until 4 weeks postgrafting. Grafted VP and VIP cells were always located together, whereas SOM cells were clustered nearby but separate. Neuropeptide Y fibers were observed with an increasing fiber density between 2 and 5 weeks posttransplantation and were clustered particularly at the level of the SOM cells. In all rhythm-recovered animals transplants of VP and VIP fibers had grown laterally into the hypothalamus. A few nonrecovered animals also showed ingrowth of such fibers, though more caudally to the lesioned SCN. Many of the nonrecovered rats showed similar stainings but without these efferent outgrowth to the host. We conclude that neither a humoral factor nor the presence of VP and VIP efferents in the host brain alone are enough for the restoration of circadian drinking rhythms.
Animals↗
Circadian rhythms and masking: an overview.
Masking, as is well known, enables an organism to act immediately and in an appropriate way to changes of the environment, integrating with internally produced rhythmicity. It now appears that masking can be used to cover a far wider range of problems than was originally intended. To separate masking effects from the effects due to an internal oscillator, several techniques have been used. Such protocols, however, like the constant routine protocol, often replace one form of masking by another. The situation becomes even more complex when one realizes that the output of an internal oscillator modifies the input. The question might be asked whether it is possible to study the properties of the internal oscillator in vivo at all. This article attempts to produce a framework for future discussions.
Adaptation, Physiological↗
Chronobiology: neural pacemakers of biological rhythms.
Biological rhythms are ubiquitous being demonstrable of any level of organization in living matter. However, the myriad of biological oscillators in peripheral organs are organized and synchronized by special structure, i.e., biological clocks, mostly located in central nervous system. Neural pacemakers show intrinsic properties which are illustrated and discussed. Understanding the meaning and function of neural oscillators is fundamental for those who wants to know how the biological structure of time is processed in living systems.
Animals↗
Spontaneous and stimulated firing in cultured rat suprachiasmatic neurons.
Neurons from the suprachiasmatic nucleus (SCN) of the hypothalamus, the site of a circadian pacemaker in mammals, were isolated from embryonic rat. After mechanical dissociation neurons were brought into culture for 1-2 weeks, using a chemically defined medium. Recordings were made from 74 bipolar neurons using two different configurations of the patch-clamp technique. During cell attached patch recordings, 45% of neurons fired spontaneously. The mean firing rate was 0.7 +/- 0.6 Hz and the firing pattern was irregular. In whole cell recordings 73% of the investigated neurons showed spontaneous activity with an irregular firing pattern. The mean spontaneous firing rate with an intracellular Cl- concentration of 145 mM was 1.0 +/- 0.6 Hz. The resting membrane potential of the bipolar neurons was estimated to be -62 +/- 24 mV. An intracellular Cl- concentration of 145 mM depolarised the membrane potential. It also increased the probability of spontaneous firing. A depolarising current stimulus produced an action potential with a threshold voltage of -46 +/- 9 mV. Suprathreshold stimuli resulted in repetitive firing with a mean frequency of 12 +/- 4 Hz. The minimum interspike interval was 52 +/- 14 ms. All action potentials either occurring spontaneously or elicited by current stimuli were abolished by the Na(+)-channel blocker TTX. These results indicate that our cultured neurons have some electrophysiological properties in common with SCN neurons in brain slices and in vivo.
Action Potentials↗
Neurotransmitters and the pharmacology of the suprachiasmatic nuclei.
The suprachiasmatic nucleus is the major component of the biological clock responsible for the generation and the regulation of circadian rhythms in behavioral and physiological functions. The SCN acts as an endogenous circadian pacemaker that becomes entrained to the light/dark cycle. Although many neuropeptides and neurotransmitters have been localized within and around the SCN, their role in the generation of the circadian signal still has to be elucidated. There are some data about the transmitters that are involved in the mechanism of entrainment. The way the SCN modulates the homeostatic control systems that are involved in the control of behaviour, also needs more clarification.
Animals↗
Prediction of various grades of cervical neoplasia on plastic-embedded cytobrush samples. Discriminant analysis with qualitative and quantitative predictors.
The purpose of this study was to investigate whether discrimination into five groups of various grades of cervical preneoplasia and neoplasia is possible using discriminant analysis models. Data were analyzed for 242 cases diagnosed as either slight dysplasia (n = 50), moderate dysplasia (n = 50), severe dysplasia (n = 50), carcinoma in situ (n = 50) or invasive carcinoma (n = 42) and consisted of qualitative and quantitative features of cells derived from a repeat sample taken from the ectocervix as well as the endocervix using Cytobrushes. The samples were embedded in plastic, and thin sections were prepared, resulting in a monolayer of cut nuclei. The percentages of expected correct prediction were obtained by using 10,000 double cross-validation samples; the mean percentage of correct prediction into five groups using cross-validation was 65% (in the original analysis, 72%) and into two groups (dysplasia versus carcinoma in situ and invasive carcinoma) was 91% (93%). The results reflect group discrimination potential; we do not claim reliability of prediction for an individual patient. The patients were not a representative sample of the population; to investigate whether groups of patients could be discriminated on the basis of both qualitative and quantitative features, the data analyzed contain an almost equal number of observations in each of the five groups. The results indicate that features do not classify the cases in the same way; the discriminant analyses suggest that quantitative features play an important role in the discrimination of dysplasia from carcinoma cases, while the majority of the qualitative features are important in discrimination within the three dysplasia groups.
Biopsy↗
Properties of parametric photic entrainment of circadian rhythms in the rat.
Wistar rats were exposed to 24-h cycles of sinusoidal varying light intensity at various amplitudes (A) and mean intensity (I) levels. The cycle minimum was at least 0.1 lux. Food approaches and wheel running activity were continuously recorded. Entrainment was observed to light cycles with amplitudes as low as 2 lux. The success of entrainment increased with A and decreased with I, and loss of entrainment was accompanied by relative coordination. In a separate experiment, we measured the freerunning period (tau) in constant light at various I levels. The tau-illuminance curve was pseudolinear at low I (above 0.1 lux) and saturated at high I (above 100 lux). The intensity dependence of tau corresponded to the intensity response characteristics of light responsive cells in the rat suprachiasmatic nuclei, as published by other authors. It was hypothesized that the light responsive cells mediate the parametric effects of constant light and of sine waves of light.
Animals↗
Effects of T cycles of light/darkness and periodic forced activity on methamphetamine-induced rhythms in intact and SCN-lesioned rats: explanation by an hourglass-clock model.
In this study intact and suprachiasmatic nuclei (SCN)-lesioned female rats were treated with chronic methamphetamine (MA) via the drinking water. Body temperature, feeding, drinking and wheel-running activity were continuously and automatically recorded. The rats were subjected to light-dark (LD) cycles with period T = 23 hr for 4 months and subsequently T = 25 hr for 3 months. Daily 3-hr forced activity (FA 3:21) was imposed during a few weeks under both LD regimes. MA induced infradian rhythms (period tau s = 28-54 hr) that were found to run parallel in all functions. In intact rats these infradian rhythms showed relative coordination by the LD regime and tau s shortened when T lengthened. In SCN-lesioned rats, however, the infradian rhythms were independent of the LD regime. Under the FA cycles tau s lengthening as well as synchronization was observed. We hypothesized that the MA-induced rhythms reflect a long-period sleep-wake cycle of the hourglass type. We investigated this hypothesis with a modified version of the hourglass-clock model of sleep regulation. Computer simulations showed that this model might offer an explanation for the experimental observations.
Animals↗
Effect of regular 3-yearly screening on the incidence of cervical smears: the Leiden experience.
The effect of regular 3-yearly screening over a period of 12 years, on the incidence of cervical cancer in 25,000 women aged 35-54 years, is examined. The rate of squamous cell carcinoma decreased from 0.38 per 1000 women in the first round to zero in the fourth round. Similarly, the rate of carcinoma in situ declined from 1.69 per 1000 women in the first round to 0.35 per 1000 in the fourth round. The rates of severe dysplasia showed no decline. Cytologic under diagnosis of carcinoma-in-situ and cervical carcinoma increased with each round. Widowed and divorced women and those living in urban areas were identified as high risk groups.
Adenocarcinoma↗
Chronobiology.
The field of chronobiology, the study of the rhythms in plants and animals, was restricted to botanists for centuries. Only recently during the last decades could research be broadened to include animals and later even human beings. Rhythms have been documented and related to the alternation of day and night and to the succession of the seasons. Nowadays, chronobiology has developed into a multidisciplinary field in which scientists are involved in basic research as well as in applied topics. This paper gives an introduction to the field, especially dealing with the aspect of rhythm development, and the way in which the different 24-hour rhythms in children become apparent.
Adult↗
The central control and ontogeny of circadian rhythmicity.
The field of Chronobiology, the study of the rhythms in plants and animals, was restricted to botanists for centuries. Only recently during the last decades research could be broadened to include animals and later even human beings. Rhythms have been documented and related to the alternation of day and night and to the succession of the seasons. Nowadays chronobiology has developed into a multidisciplinary field in which scientists are involved in basic research as well as in applied topics. This paper gives an introduction to the field, especially dealing with the aspect of rhythm development and the way in which the different 24 hour rhythms in children become apparent.
Aging↗
The suprachiasmatic nucleus of the rat hypothalamus in culture: an anatomical and electrophysiological study.
This study shows that foetal neurons from the suprachiasmatic area, after dissociation and culture, contain in vitro the same characteristics as are found in the in vivo situation. The main peptidergic neurotransmitters present in the suprachiasmatic nucleus in vivo, vasoactive intestinal polypeptide (VIP) and vasopressin, are expressed in vitro while the cytoskeleton of these cells possesses phosphorylated neurofilaments. The exclusive uptake of Lucifer Yellow liposomes by neurons is also refound in suprachiasmatic cultures. The electrophysiological results are in agreement with those characteristics found in vitro and in vivo.
Action Potentials↗
Effects of time of feeding on recovery of food-entrained rhythms during subsequent fasting in SCN-lesioned rats.
Rats subjected to Eat-Fast (EF) cycles show food-anticipatory rhythms independent from the suprachiasmatic nuclei (SCN). These rhythms do not persist during subsequent ad lib feeding (EE). There are indications for a recovery of rhythmicity during fasting (FF) using a 'memory' paradigm in which FF sessions are alternated with EE. In this study we tested the memory paradigm in SCN-lesioned rats that were fed for 3 hr either during the local day (food access at 14.30 hr) or during the night (food access at 04.30 hr or at 23.00 hr). Food approaches, drinking, wheel-running and body temperature were recorded under constant light. Food-anticipatory rhythms emerged under each EF schedule while the shape of the rhythms differed per schedule. The rhythms disappeared in EE. During subsequent FF the rhythms clearly reappeared in previously day-fed rats, but this was only occasionally observed in previously night-fed rats. Moreover, the phase of the rhythms which did recover in the previously night-fed rats was shifted towards daytime. These data are not fully compatible with the hypothesis of a self-sustained food-entrainable oscillator. It was assumed that hunger-induced responses to environmental daytime stimuli contributed to the overt rhythms.
Animals↗