Tom Deboer

Leiden University Medical Centre | LUMC · Department of Cell and Chemical Biology

Acute effects of exogenous melatonin have been widely reported to promote sleep or induce drowsiness in human. However, testing of the hypnotic effects of melatonin in nocturnal rodents has yielded contradictory results. The latter may be associated with differences in concentration, lighting conditions, time of administration of melatonin, and pos...

Different mouse strains used in biomedical research show different phenotypes associated with their genotypes. Two mouse strains commonly used in biomedical sleep research are C57Bl/6 and C3H/He, the strains differ in numerous aspects, including their ability to secrete melatonin as well as the expression of several sleep‐related genes. However, sl...

Ketamine is known for its antidepressant effects, but the mechanism underlying this effect remains largely unclear. In contrast to most antidepressant drugs, the action of ketamine is rapid, suggesting a different mode of action. A rapid antidepressant effect is also observed following sleep deprivation (SD). In the present study, we aimed to evalu...

Sleep/wake alterations are predominant in neurological and neuropsychiatric disorders involving dopamine dysfunction. Unfortunately, specific, mechanisms‐based therapies for these debilitating sleep problems are currently lacking. The pathophysiological mechanisms of sleep/wake alterations within a hypodopaminergic MitoPark mouse model of Parkinson...

The central circadian clock, located in the suprachiasmatic nucleus (SCN) within the brain, regulates daily patterns of activity and physiology. Many studies indicate that exercise at specific times throughout the day can help maintain proper circadian rhythms. In nocturnal animals, even moderate levels of physical activity suppress the neuronal di...

The European Somnologist certification programme was developed by the European Sleep Research Society to improve patient care in sleep medicine by providing an independent evaluation of theoretical and practical knowledge. The examination of eligible experts plays a key role in this procedure. A process was started more than 15 years ago to create...

Background: Caffeine is a central nervous system stimulant that influences both the sleep-wake cycle and the circadian clock and is known to influence neuronal activity in the lateral hypothalamus, an important area involved in sleep-wake regulation. Light is a strong zeitgeber and it is known to interact with the effect of caffeine on the sleep-w...

Cancer-related fatigue (CRF) is the most devastating long-term side effect of many cancer survivors that confounds the quality of life for months to years after treatment. However, the cause of CRF is poorly understood. As a result, cancer survivors, at best, receive psychological support. Chemotherapy has been shown to increase the risk of CRF. He...

For hundreds of years, mankind has been influencing its sleep and waking state through the adenosinergic system. For ~100 years now, systematic research has been performed, first started by testing the effects of different dosages of caffeine on sleep and waking behaviour. About 70 years ago, adenosine itself entered the picture as a possible ligan...

It is 50 years ago, in 1972, that the founding conference of the European Sleep Research Society (ESRS) was organised in Basel. Since then the Society has had 13 presidents and a multitude of board members and has organised, among other things, another 24 congresses. At this 50th anniversary, as the 26th ESRS congress is approaching, we have summar...

Sleep deprivation reduces the response of neuronal activity in the suprachiasmatic nucleus (SCN) and the phase shift in circadian behaviour to phase shifting light pulses, and thus seems to impair the adaptation of the circadian clock to the external light-dark cycle. The question remains where in the pathway of light input to the SCN the response...

The human sleep-wake cycle is tightly coupled to the circadian time course of CBT. The evening increase in heat loss through distal skin regions and reduction in heat production is associated with sleepiness and the ease of falling asleep. After sleep initiation, ultradian NREM/REM sleep cycle fluctuations seem to have minor thermoregulatory functi...

Objectif L’ensemble des fonctions rythmiques est orchestré par les noyaux suprachiasmatiques (SCN). Chez l’Arvicanthis, un rongeur diurne, l’activité locomotrice augmente l’activité neuronale des SCN. Nombreux travaux ont montré l’existence d’interactions réciproques entre activité locomotrice et sérotonine, impliquée à la fois, dans la synchronisa...

Basal Ganglia (BG) are a set of subcortical nuclei that are involved in the control of a wide variety of motor, cognitive and affective behaviors. Although many behavioral abnormalities associated with BG dysfunction overlap with the clinical picture precipitated by the lack of sleep, the impact of sleep alterations on neuronal activity in BG is un...

We have recently identified a novel plasticity protein, doublecortin-like (DCL), that is specifically expressed in the shell of the mouse suprachiasmatic nucleus (SCN). DCL is implicated in neuroplastic events, such as neurogenesis, that require structural rearrangements of the microtubule cytoskeleton, enabling dynamic movements of cell bodies and...

Circadian organization of physiology and behavior is an important biologic process that allows organisms to anticipate and prepare for predictable changes in the environment. Circadian disruptions are associated with a wide range of health issues. In patients with neurodegenerative diseases, alterations of circadian rhythms are among the most commo...

Aging is a multifactorial process likely stemming from damage accumulation and/or a decline in maintenance and repair mechanisms in the organisms that eventually determine their lifespan. In our review, we focus on the morphological and functional alterations that the aging brain undergoes affecting sleep and the circadian clock in both human and r...

In humans, the evening increase in heat loss through distal skin regions and the reduction in heat production are clearly influenced by the circadian clock and associated with the ease to fall asleep. In contrast, a homeostatic increase in sleep pressure, even during moderate sleep deprivation does not seem to influence the thermoregulatory system....

In humans, the evening increase in heat loss through distal skin regions and the reduction in heat production are clearly influenced by the circadian clock and associated with the ease to fall asleep. In contrast, a homeostatic increase in sleep pressure, even during moderate sleep deprivation does not seem to influence the thermoregulatory system....

Prevalence rates of attention-deficit/hyperactivity disorder (ADHD) differ with geographical areas varying in sunlight intensity. Sun- or daylight reaching the retina establishes entrainment of the circadian clock to daylight. Changes herein, hence, alterations in clock alignment, could be reflected indirectly in inattention via sleep duration. We...

Artificial light, despite its widespread and valuable use, has been associated with deterioration of health and well-being, including altered circadian timing and sleep disturbances, particularly in nocturnal exposure. Recent findings from our lab reveal significant sleep and sleep electroencephalogram (EEG) changes owing to three months exposure t...

Dim-light-at-night (DLAN) exposure is associated with health problems, such as metabolic disruptions, immunological modulations, oxidative stress, sleep problems, and altered circadian timing. Neurophysiological parameters, including sleep patterns, are altered in the course of aging in a similar way. Here, we investigated the effect of chronic (th...

Sleep is one of the many behaviours that is under the control of the circadian clock. Sleep is regulated by different brain regions, distributed over two major regulatory systems. The ascending reticular arousal system induces waking and alertness, whereas the ventrolateral preoptic area (VLPO) is thought to induce sleep. Consolidation of sleep and...

Disruption of circadian rhythm by means of shift work has been associated with cardiovascular disease in humans. However, causality and underlying mechanisms have not yet been established. In this study, we exposed hyperlipidemic APOE*3‐Leiden.CETP mice to either regular light‐dark cycles, weekly 6 h phase advances or delays, or weekly alternating‐...

Prevalence rates of Attention-Deficit/Hyperactivity Disorder (ADHD) differ with geographical areas varying in sunlight intensity. We here studied 1) annual variation in inattention at treatment initiation; 2) annual variation in response to ADHD treatment [Methylphenidate (MPH)] by day of treatment initiation; and 3) dose-dependency. We predicted l...

Disturbance of the circadian clock has been associated with increased risk of cardio-metabolic disorders. Previous studies showed that optimal timing of food intake can improve metabolic health. We hypothesized that time-restricted feeding could be a strategy to minimize long term adverse metabolic health effects of shift work and jetlag. In this s...

Obesity and sleep disturbances comprise major health problems which are likely interrelated. Diet-induced obesity in young mice has been demonstrated to lead towards an altered sleep homeostasis. In the current study, we investigated the effect of chronic (12 weeks) high-caloric diet (HCD, 45% fat) consumption on sleep and the sleep electroencephal...

Background:: Caffeine is one of the most widely consumed psychostimulants, and it impacts sleep and circadian physiology. Aim:: Caffeine is generally used chronically on a daily basis. Therefore, in the current study, we investigated the chronic effect of caffeine on sleep in mice. Methods:: We recorded the electroencephalogram and electromyog...

Physical activity is beneficial for health. It has been shown to improve brain functioning and cognition, reduce severity of mood disorders, as well as facilitate healthy sleep and healthy aging. Sleep has been studied in healthy aged mice and absolute slow-wave-activity levels (SWA, electroencephalogram power between 0.75 and 4.0 Hz) in non-rapid-...

Although the link between sleep disturbances and dopamine (DA)-related neurological and neuropsychiatric disorders is well established, the impact of sleep alterations on neuronal activity of midbrain DA-ergic structures is currently unknown. Here, using wildtype C57Bl mice, we investigated the circadian- and sleep-related modulation of electrical...

Obesity prevalence and sleep habit changes are commonplace nowadays, due to modern lifestyle. A bidirectional relationship likely exists between sleep quality and metabolic disruptions, that could impact quality of life. In our study, we investigated the effects of a chronic high‐caloric diet on sleep architecture and sleep regulation in mice. We s...

The Lateral Hypothalamus (LH) is a relatively large hypothalamic structure containing several neurochemically different, but spatially intermingled, neuronal populations. While the role of these neurons in the homeostatic regulation of diverse physiological and behavioural functions such as sleep/wake cycle has been studied extensively, the impact...

Sleep is regulated by a homeostatic and a circadian process. Together these two processes determine most aspects of sleep and related variables like sleepiness and alertness. The two processes are known to be able to work independently, but also to both influence sleep and sleep related variables in an additive or more complex manner. The question...

Lack of adequate sleep has become increasingly common in our 24/7 society. Unfortunately diminished sleep has significant health consequences including metabolic and cardiovascular disease and mental disorders including depression. The pathways by which reduced sleep adversely affects physiology and behavior are unknown. We found that 6h of sleep d...

Changes in sleep pattern are typical for the normal aging process. However, aged mice show an increase in the amount of sleep, whereas humans show a decrease when aging. Mice are considered an important model in aging studies, and this divergence warrants further investigation. Recently, insights into the network dynamics of cortical activity durin...

It has been shown previously in Djungarian hamsters that the initial electroencephalography (EEG) slow-wave activity (power in the 0.5–4.0 Hz band; SWA) in non-rapid eye movement (NREM) sleep following an episode of daily torpor is consistently enhanced, similar to the SWA increase after sleep deprivation (SD). However, it is unknown whether the ne...

Exposure to light at night (LAN) is associated with insomnia in humans. Light provides the main input to the master clock in the hypothalamic suprachiasmatic nucleus (SCN) that coordinates the sleep-wake cycle. We aimed to develop a rodent model for the effects of LAN on sleep. Therefore, we exposed male Wistar rats to either a 12 h light (150–200l...

In the last three decades the two-process model of sleep regulation has served as a major conceptual framework in sleep research. It has been applied widely in studies on fatigue and performance and to dissect individual differences in sleep regulation. The model posits that a homeostatic process (Process S) interacts with a process controlled by t...

The increased prevalence of metabolic disorders and obesity in modern society, together with the widespread use of artificial light at night, have led researchers to investigate whether altered patterns of light exposure contribute to metabolic disorders. This article discusses the experimental evidence that perturbed environmental cycles induce rh...

Parkinson disease is one of the neurodegenerative diseases that benefited the most from the use of non-human models. Consequently, significant advances have been made in the symptomatic treatments of the motor aspects of the disease. Unfortunately, this translational success has been tempered by the recognition of the debilitating aspect of multipl...

To the Editor The regulation of sleep-wakefulness behavior involves 2 physiological processes. A circadian process, based in the suprachiasmatic nucleus, is responsible for the timing of sleep and wakefulness, and a homeostatic process that monitors and responds to the quality and quantity of prior sleep and wakefulness.¹ In patients with Parkinson...

Caffeine is the most commonly used psychoactive stimulant worldwide. It reduces sleep and sleepiness by blocking access to the adenosine receptor. The level of adenosine increases during sleep deprivation, and is thought to induce sleepiness and initiate sleep. Light-induced phase shifts of the rest–activity circadian rhythms are mediated by light-...

The suprachiasmatic nucleus (SCN) adapts to both the external light-dark (LD) cycle and seasonal changes in day length. In short photoperiods, single-cell activity patterns are tightly synchronized (i.e., in phase); in long photoperiods, these patterns are relatively dispersed, causing lower amplitude rhythms. The limit cycle oscillator has been us...

The human sleep–wake cycle is usually tightly coupled to the circadian time course of core body temperature. The circadian regulation of heat loss in the evening, via distal skin regions, is intimately associated with sleepiness and the ease to fall asleep. The rise in distal heat loss and reduction in heat production during lying down and relaxing...

The definition of what sleep is depends on the method that is applied to record sleep. Behavioral and (electro)-physiological measures of sleep clearly overlap in mammals and birds , but it is often unclear how these two relate in other vertebrates and invertebrates. Homeostatic regulation of sleep, where the amount of sleep depends on the amount o...

More than half of the elderly in today's society suffer from sleep disorders with detrimental effects on brain function, behavior, and social life. A major contribution to the regulation of sleep stems from the circadian system. The central circadian clock located in the suprachiasmatic nucleus of the hypothalamus is like other brain regions subjec...

Adenosine modulates sleep via A(1) and A(2A) receptors. As the A(1) receptor influences Ca(V)2.1 channel functioning via G-protein inhibition, there is a possible role of the Ca(V)2.1 channel in sleep regulation. To this end we investigated transgenic Cacna1a R192Q mutant mice that express mutant Ca(V)2.1 channels that are less susceptible to inhib...

The mammalian central circadian pacemaker (the suprachiasmatic nucleus, SCN) contains thousands of neurons that are coupled through a complex network of interactions. In addition to the established role of the SCN in generating rhythms of ,24 hours in many physiological functions, the SCN was recently shown to be necessary for normal self-similar/f...

Effects of missing data and down-sampling on the detrended fluctuation analysis. (DOC)

Persistent circadian rhythmicity and reduced ultradian fluctuations in the in vitro SCN neural activity. (DOC)

Information of SCN slices and corresponding in vitro recordings from 7 mice. (DOC)

Deviation of the fluctuation function, F(n), from power-law fit. (A) Fluctuation functions of two individual mice (one for in vivo and one for in vitro recordings) and two rats (one for in vivo and one for in vitro recordings). The black solid line is the power-law fit for the in vivo mouse data and the red dashed line is for the in vitro mouse dat...

Testing of power-law form. (DOC)

Fractal or non-fractal fluctuations in the in vitro SCN neural activity? (DOC)

The non-fractal fluctuation pattern of the in vitro SCN activity is independent of the size of the SCN slice. Shown are the detrended fluctuation functions of 3 SCN slices that contained 90%, 70% and 40% of the SCN in the rostro-caudal plane, respectively (mouse 6, 4, and 3 in Table S1, respectively). The scaling curves were vertically shifted to b...

Detrended fluctuation function of in vitro MUA during different 12-hour periods. The in vitro MUA recording was ∼40 hours in duration (shown in Figure 1A) and started ∼1 hour after harvesting the SCN. The fluctuation function F(n) was similar for all 12-hour periods. Shuffling MUA data destroyed the correlations in the signal, leading to a white-no...

Fractal patterns of motor activity in mice. (DOC)

Sleep is regulated by circadian and homeostatic processes. The sleep homeostat keeps track of the duration of prior sleep and waking and determines the intensity of sleep. In mammals, the homeostatic process is reflected by the slow waves in the non-rapid eye movement (NREM) sleep electroencephalogram (EEG). The circadian process is controlled by a...

People with attention-deficit/hyperactivity disorder (ADHD) often experience sleep problems, and these are frequently exacerbated by the methylphenidate they take to manage their ADHD symptoms. Many of the changes to sleep are consistent with a change in the underlying circadian clock. The present study was designed to determine if methylphenidate...

Aging is associated with a deterioration of daily (circadian) rhythms in physiology and behavior. Deficits in the function of the central circadian pacemaker in the suprachiasmatic nucleus (SCN) have been implicated, but the responsible mechanisms have not been clearly delineated. In this report, we characterize the progression of rhythm deteriorat...

The human sleep-wake cycle is usually tightly coupled to the circadian time course of core body temperature. The circadian regulation of heat loss in the evening, via distal skin regions, is intimately associated with sleepiness and the ease to fall asleep, whereas the homeostatic increase in sleep pressure does not influence the thermoregulatory s...

Similar to the nap-protocols applied in humans, the repeated short-sleep deprivation protocol in rats stabilizes slow-wave activity (SWA, 0.5-4 Hz) in the non-rapid eye movement (NREM) sleep electroencephalogram (EEG), thus reflecting a constant sleep pressure or sleep homeostatic level, whereas higher frequencies (7-25 Hz) in these conditions pres...

Circadian rhythms govern many aspects of physiology and behavior including cognitive processes. Components of neural circuits involved in learning and memory, e.g., the amygdala and the hippocampus, exhibit circadian rhythms in gene expression and signaling pathways. The functional significance of these rhythms is still not understood. In the prese...

Sleep is regulated by homeostatic and circadian processes. Slow wave activity (SWA; 1-4 Hz) in the NREM sleep electroencephalogram (EEG) reflects sleep homeostasis. Activity of faster EEG frequencies (10-25 Hz) is thought to be under influence of circadian factors. The relative contribution of both processes to the distribution of sleep and wakeful...

The circadian distribution of vigilance states and body temperature changes are tightly coupled. The increase in heat loss at the end of the day is associated with increased ease to fall asleep. Experimental data show that warming the skin or the brain can increase sleep propensity, sleep consolidation, and the duration of sleep. Anatomical and neu...

The SCN of the hypothalamus contains a major pacemaker, which exhibits 24-h rhythms in electrical impulse frequency. Although it is known that SCN electrical activity is high during the day and low during the night, the precise relationship between electrical activity and behavioral rhythms is almost entirely unknown. The authors performed long-ter...

According to the two-process model of sleep regulation, a homeostatic Process S increases during waking and decreases during sleep. The time course of Process S can be derived on the basis of changes in vigilance states and changes in electroencephalogram slow-wave activity (SWA, activity below 4 Hz) during non-rapid eye movement (NREM) sleep. In m...

Mammalian circadian rhythms are driven by the circadian pacemaker of the suprachiasmatic nucleus (SCN) and are synchronized to the external 24-hour light/dark cycle. After advance time zone transitions (eastbound jet lag), overt circadian rhythms require several days to adjust. The retarded adaptation may protect against acute imbalance of differen...

Circadian rhythms are a common characteristic ofmulticellular organisms and evolved as an adaptation to the earth's rotation on its axis. In humans, circadian rhythms are regulated by suprachiasmatic nuclei located at the base of the hypothalamus. The suprachiasmatic nuclei function as a biological clock that controls the daily rhythms of nearly al...