Irene Tobler

Irene Tobler
University of Zurich | UZH · Institute for Pharmacology and Toxikology

PhD

About

199
Publications
30,614
Reads
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13,490
Citations
Citations since 2016
3 Research Items
3208 Citations
20162017201820192020202120220100200300400
20162017201820192020202120220100200300400
20162017201820192020202120220100200300400
20162017201820192020202120220100200300400
Additional affiliations
October 1975 - January 2017
University of Zurich
Position
  • Head of Department

Publications

Publications (199)
Article
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...
Article
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The amount and architecture of vigilance states are governed by two distinct processes, which occur at different time scales. The first, a slow one, is related to a wake/sleep dependent homeostatic Process S, which occurs on a time scale of hours, and is reflected in the dynamics of NREM sleep EEG slow-wave activity. The second, a fast one, is mani...
Article
This chapter introduces a two-process model and highlights that a homeostatic process (process S) rises during waking and declines during sleep. It interacts with a circadian process (process C) that is independent of sleep and waking. The time course of the homeostatic variable S was derived from electroencephalographic (EEG) SWA. Different aspect...
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Autoimmune and infectious diseases are associated with behavioral changes referred to as sickness behavior syndrome (SBS). In autoimmunity, the generation of anti-self T lymphocytes and autoantibodies critically involves binding of CD40 ligand on T-cells to its receptor CD40 on B-cells, dendritic cells and macrophages. Activation of CD40 leads to p...
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Sleep and sleep intensity are enhanced by adenosine and its receptor agonists, whereas adenosine receptor antagonists induce wakefulness. Adenosine kinase (ADK) is the primary enzyme metabolizing adenosine in adult brain. To investigate whether adenosine metabolism or clearance affects sleep, we recorded sleep in mice with engineered mutations in A...
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Study Objectives The main energy reserve of the brain is glycogen, which is almost exclusively localized in astrocytes. We previously reported that cerebral expression of certain genes related to glycogen metabolism changed following instrumental sleep deprivation in mice. Here, we extended our investigations to another set of genes related to glyc...
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The main energy reserve of the brain is glycogen, which is almost exclusively localized in astrocytes. We previously reported that cerebral expression of certain genes related to glycogen metabolism changed following instrumental sleep deprivation in mice. Here, we extended our investigations to another set of genes related to glycogen and glucose...
Article
We thank Dr. Feinberg and colleagues for their thoughtful comments on [25]. In that paper we found that, in awake mice, the global brain uptake of 2-deoxyglucose (2-DG) was higher if the animals had been previously awake than if they slept prior to sacrifice. Our data were consistent with a human study showing reduced cerebral blood flow after a ni...
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There is increasing evidence that sleep facilitates memory acquisition and consolidation. Moreover, the sleep-wake history preceding memory acquisition and retention as well as circadian timing may be important. We showed previously that sleep deprivation (SD) following learning in OF1 mice impaired their performance on an object recognition task....
Article
In recent years, sleep medicine has evolved into a full-grown discipline, featuring a multidisciplinary approach to diagnosis and treatment of patients with sleep disorders. Sleep medicine cuts across the boundaries of different conventional disciplines and is therefore open to medical and non-medical professionals with different specialty backgrou...
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Caffeine is believed to exert its stimulant effects by blocking A(2A) and A(1) adenosine receptors (A(2A)R and A(1)R). Although a genetic knockout of A(2A)R eliminates effects of caffeine, the phenotype of the knockout animal does not resemble that of caffeine treatment. In this study we explored the possibility that a mere reduction of the number...
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Caffeine is believed to exert its stimulant effects by blocking A(2A) and A(1) adenosine receptors (A(2A)R and A(1)R). Although a genetic knockout of A(2A)R eliminates effects of caffeine, the phenotype of the knockout animal does not resemble that of caffeine treatment. In this study we explored the possibility that a mere reduction of the number...
Article
Thalamo-cortical networks generate specific patterns of oscillations during distinct vigilance states and epilepsy, well characterized by electroencephalography (EEG). Oscillations depend on recurrent synaptic loops, which are controlled by GABAergic transmission. In particular, GABAA receptors containing the α3 subunit are expressed predominantly...
Article
A recent hypothesis suggests that a major function of sleep is to renormalize synaptic changes that occur during wakefulness as a result of learning processes [G. Tononi, C. Cirelli, Sleep and synaptic homeostasis: a hypothesis, Brain Res. Bull. 62 (2003) 143-150; G. Tononi, C. Cirelli, Sleep function and synaptic homeostasis, Sleep Med. Rev. 10 (2...
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Sleep electroencephalographic (EEG) slow-wave activity is increased after wakefulness and decreases during sleep. Regional sleep EEG differences are thought to be a consequence of activation of specific cortical neuronal circuits during waking. We investigated the relationship between handedness and interhemispheric brain asymmetry. Bilateral EEG r...
Article
Sleep is regulated by the interaction of a homeostatic (Process S) and a circadian component. The duration of prior wakefulness is the main factor influencing subsequent sleep duration and its intensity. We investigated in the rat whether the sleep-wake history before sleep deprivation (SD) contributes to the effects of sleep loss incurred during t...
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Production of TNF-α and IL-1 in infectious and autoimmune diseases is associated with fever, fatigue, and sleep disturbances, which are collectively referred to as sickness behavior syndrome. In mice TNF-α and IL-1 increase nonrapid eye movement sleep. Because clock genes regulate the circadian rhythm and thereby locomotor activity and may alter sl...
Article
We tested the hypothesis that the effects of GABAergic agonists on behavior and the electroencephalogram (EEG) result from an increased regional synchronization in cortical circuits. The relationship between regional EEG topography, EEG synchronization and alteration of behavior was investigated by administering male C57BL/6 mice (n=7) a high, 3 mg...
Article
THIP (4,5,6,7-tetrahydroisoxazolo-[5,4-c]pyridine-3-ol, Gaboxadol) is a selective gamma-aminobutyric acid (GABA)(A) agonist, acting in vitro with high potency and efficacy at the extrasynaptic GABA(A)delta-containing receptors. THIP was suggested to be a potential hypnotic to treat insomnia, and it is currently in clinical trial. Here we assessed w...
Article
The effect of circulating oestrogen deficiency on sleep regulation and locomotor activity was investigated in aromatase cytochrome P450 deficient mice (ArKO) and wild-type (WT) controls. Sleep was recorded in 3-month old mice during a 24-h baseline day, 6-h sleep deprivation (SD) and 18-h recovery, and activity was recorded at the age of 3, 9 and 1...
Article
The principal objective of this study was to establish whether mice can convert melatonin to 6-sulphatoxymelatonin (aMT6s). Precision-cut liver slices from C3H/He, C57BL/6, and BALB/c mice were incubated with melatonin, and the concentration of aMT6s in the culture media was determined using a sensitive and specific radioimmunoassay procedure. All...
Article
The prevalence and characteristics of sleep-wake disturbances in sporadic Creutzfeldt-Jakob disease (sCJD) are poorly understood. Seven consecutive patients with definite sCJD underwent a systematic assessment of sleep-wake disturbances, including clinical history, video-polysomnography, and actigraphy. Extent and distribution of neurodegeneration...
Article
Many studies in animals and humans suggest that sleep facilitates learning, memory consolidation, and retrieval. Moreover, sleep deprivation (SD) incurred after learning, impaired memory in humans, mice, rats, and hamsters. We investigated the importance of sleep and its timing in an object recognition task in OF1 mice subjected to 6h SD either imm...
Article
It is now well known that daily torpor induces a sleep deficit. Djungarian hamsters emerging from this hypometabolic state spend most of the time in sleep. This sleep is characterized by high initial values of EEG slow-wave activity (SWA) that monotonically decline during recovery sleep. These features resemble the changes seen in numerous species...
Article
Despite the widespread use of inbred mice in research, little is known about aging of the circadian system in female mice, although interactions between female gonadal hormones and circadian rhythms have been established. We investigated the influence of the estrus cycle on circadian aspects of running-wheel activity and changes in the course of ag...
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Regional aspects of sleep homeostasis were investigated in mice provided with a running wheel for several weeks. Electroencephalogram (EEG) spectra of the primary motor (frontal) and somatosensory cortex (parietal) were recorded for three consecutive days. On a single day (day 2) the wheel was locked to prevent running. Wheel running correlated neg...
Article
Sleep has been shown to play a facilitating role in memory consolidation, whereas sleep deprivation leads to performance impairment both in humans and rodents. The effects of 4-h sleep deprivation on recognition memory were investigated in the Djungarian hamster (Phodopus sungorus). Because sleep during the first hours after daily torpor has many s...
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Topographic differences in the sleep EEG have been repeatedly found in humans and rodents. A frontal predominance of EEG slow-wave activity (0.75-4 Hz; delta band) during non-rapid eye movement (NREM) sleep is particularly evident under conditions of increased sleep propensity. Local aspects of neuronal connectivity in the neocortex that are modifi...
Article
In humans, EEG power in the theta frequency band (5-8 Hz) during quiet waking increases during sleep deprivation (SD), and predicts the subsequent homeostatic increase of sleep slow-wave activity (SWA; EEG power between 0.5 and 4.0 Hz). These findings indicate that theta power in waking is an EEG variable, which reflects the rise in sleep propensit...
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Sleep deprivation is accompanied by the progressive development of an irresistible need to sleep, a phenomenon whose mechanism has remained elusive. Here, we identified for the first time a reflection of that phenomenon in vitro by showing that, after a short 2 h period of total sleep deprivation, the action of noradrenaline on the wake-promoting h...
Article
THIP is a GABA(A) agonist with hypnotic properties consisting in reducing sleep latency and prolonging and consolidating sleep. THIP has been reported to increase EEG slow-wave activity (SWA; EEG power in the 0.75-4 Hz band) in non-REM (NREM) sleep in both rats and humans. We investigated the effects of THIP on sleep in C57BL/6 mice. EEG recordings...
Article
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A huge amount of knowledge about sleep has accumulated during the last 5 decades following the discovery of rapid eye movement (REM) sleep. Nevertheless, there are numerous areas of considerable ignorance. One of these concerns the particularities of sleep in women. Most basic and clinical studies have been performed in male subjects, and only very...
Article
Zolpidem is a widely used hypnotic that binds preferentially to alpha1GABAA receptors. We determined the role of these receptors in the effects of zolpidem on sleep in mutant mice carrying zolpidem-insensitive alpha1GABAA receptors and wild-type controls. Sleep was promoted by zolpidem in both genotypes. In wild-type mice non-REM sleep EEG power wa...
Article
Regional differences in EEG slow wave activity (SWA) during sleep after sleep deprivation (SD) may be a consequence of differential metabolic activation of cortical areas. We investigated the relationship between the regional EEG dynamics and 2-deoxyglucose (DG) uptake after SD in mice. Six hours' SD were combined with natural unilateral whisker st...
Article
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A quantitative analysis of spindles and spindle-related EEG activity was performed in C57BL/6 mice. The hypothesis that spindles are involved in sleep regulatory mechanisms was tested by investigating their occurrence during 24 h and after 6 h sleep deprivation (SD; n = 7). In the frontal derivation distinct spindle events were characterized as EEG...
Article
Rab proteins are small GTPases involved in intracellular trafficking. Among the 60 different Rab proteins described in mammals, Rab3a is the most abundant in brain, where it is involved in synaptic vesicle fusion and neurotransmitter release. Rab3a constitutive knockout mice (Rab3a(-/-)) are characterized by deficient short- and long-term synaptic...
Article
Mammalian motor activity displays circadian patterns in normal behaviour and in many movement disorders, like levodopa responsive dystonia and Parkinson's disease. Here, we hypothesized that a circadian pattern of dopamine synthesis would trigger rhythms in the expression of genes in regions receiving dopaminergic innervation. Indeed tyrosine hydro...
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The inhibitory neurotransmitter gamma-aminobutyric acid (GABA) is involved in the generation of various brain rhythmic activities that can be modulated by benzodiazepines. Here, we assessed the contribution of alpha(2)GABA type A (GABA(A)) receptors to the effects of benzodiazepines on sleep and waking oscillatory patterns by combining pharmacologi...
Article
Regional differences in the effect of sleep deprivation on the sleep electroencephalogram (EEG) may be related to interhemispheric synchronization. To investigate the role of the corpus callosum in interhemispheric EEG synchronization, coherence spectra were computed in mice with congenital callosal dysgenesis (B1) under baseline conditions and aft...
Article
Full-text available
Regional differences in the effect of sleep deprivation on the sleep electroencephalogram (EEG) may be related to interhemispheric synchronization. To investigate the role of the corpus callosum in interhemispheric EEG synchronization, coherence spectra were computed in mice with congenital callosal dysgenesis (B1) under baseline conditions and aft...
Article
Sleep was investigated in 10 captive gelada baboons (Theropithecus gelada), belonging to two harem groups by continuous infrared video recording (n = 4 males, n = 3 females, n = 3 juveniles). The aim was to investigate the relation between sleep and social status. Social status was assessed during daytime activities, when the two harem groups inter...
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Full-text available
Emerging from daily torpor, Djungarian hamsters (Phodopus sungorus) show an initial increase in electroencephalographic slow-wave activity (power density between 0.75 and 4.0 Hz) during sleep that gradually declines. This feature is typical for sleep following prolonged waking and supports the hypothesis that sleep pressure increases during daily t...
Article
Benzodiazepines reduce EEG slow-wave activity in non-REM sleep by potentiating GABAergic neurotransmission at GABAA receptors via a modulatory binding site. However, the mechanisms of action underlying the effects of benzodiazepines on sleep and the sleep EEG are still unknown. Slow waves during sleep are generated by the corticothalamic system and...
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Changes in photoperiod and ambient temperature trigger seasonal adaptations in the physiology and behaviour of many species, including the Djungarian hamster. Exposure of the hamsters to a short photoperiod and low ambient temperature leads to a reduction of the polyphasic distribution of sleep and waking over the light and dark period. In contrast...
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Abstract Benzodiazepines reduce EEG slow-wave activity in non-REM sleep by potentiating GABAergic neurotransmission at GABAA receptors via a modulatory binding site. However, the mechanisms of action underlying the effects of benzodiazepines on sleep and the sleep EEG are still unknown. Slow waves during sleep are generated by the corticothalamic s...
Article
Sleep, daily torpor and hibernation are no longer considered homologous processes. Animals emerging from these states spend most of their time in sleep. After termination of the torpor-associated hypothermia, there is an initial high electroenecephalogram (EEG) slow-wave activity (SWA; 0.75-4.0 Hz) and a subsequent monotonic decline. Both of these...
Article
Full-text available
Vigilance state-related topographic variations of electroencephalographic (EEG) activity have been reported in humans and animals. To investigate their possible functional significance, the cortical EEG of the rat was recorded from frontal and parietal derivations in both hemispheres. Records were obtained for a 24-h baseline day, 6-h sleep depriva...
Article
A limited set of genes, Clock, Bmal1, mPer1, mPer2, mCry1 and mCry2, has been shown to be essential for the generation of circadian rhythms in mammals. It has been recently suggested that circadian genes might be involved in sleep regulation. We investigated the role of mPer1 and mPer2 genes in the homeostatic regulation of sleep by comparing sleep...
Article
Voltage-gated potassium channels containing the K.v.3.2 subunit are expressed in specific neuronal populations such as thalamocortical neurons and fast spiking GABAergic interneurons of the neocortex and hippocampus. These K(+)-channels play a major role in the regulation of firing properties in these neurons. We investigated whether the K.v.3.2 su...
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Full-text available
Tumor necrosis factor (TNF) and lymphotoxin-alpha (LT-alpha) are proinflammatory cytokines involved in host defense and pathogenesis of various diseases. In addition, there is evidence that TNF is involved in sleep. TNF and LT-alpha both bind to the tumor necrosis factor receptors (TNFR). Recently, it was shown that TNF receptor 1 (TNFR1) knockout...
Article
Replenishment of brain glycogen stores depleted during waking has been suggested to constitute one of the functions of sleep [Benington, J. H. & Heller H. C. (1995) Prog. Neurobiol., 45, 347]. We have tested the hypothesis that the level of expression of enzymes involved in glycogen metabolism could undergo variations throughout the sleep-waking or...
Article
Modafinil is a wakefulness-promoting substance whose profile differs from that of the classical psychostimulants. It is still unknown whether waking induced by modafinil and wakefulness induced by sleep deprivation differ in terms of their effect on subsequent sleep. To investigate this problem sleep was recorded in two groups of OF1 mice. One grou...
Article
Full-text available
Tumor necrosis factor (TNF) and lymphotoxin-α (LT-α) are proinflammatory cytokines involved in host defense and pathogenesis of various diseases. In addition, there is evidence that TNF is involved in sleep. TNF and LT-α both bind to the tumor necrosis factor receptors (TNFR). Recently, it was shown that TNF receptor 1 (TNFR1) knockout mice (R1KO)...
Article
We have previously reported a larger and more prolonged increase of slow wave activity (SWA) in NREM sleep after sleep deprivation (SD) in prion protein deficient mice (PrP) compared to wild-type mice. Regional differences in the SWA increase were investigated by comparing the effect of 6 h SD on a frontal and occipital derivation in PrP deficient...
Article
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Measurements and Results: Total sleep time (52% of recording time) and the amount of REM sleep (8% of recording time) in these subterranean rodents are in the range of values found in the laboratory rat, mouse and hamster recorded under similar conditions. In contrast to these species, the polyphasic sleep-wakefulness distribution in mole rats was...
Article
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Ligands acting at the benzodiazepine (BZ) site of gamma-aminobutyric acid type A (GABA(A)) receptors currently are the most widely used hypnotics. BZs such as diazepam (Dz) potentiate GABA(A) receptor activation. To determine the GABA(A) receptor subtypes that mediate the hypnotic action of Dz wild-type mice and mice that harbor Dz-insensitive alph...
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The mole rat, Spalax ehrenbergi, is an interesting species for sleep because of its pronounced specialization to a fossorial life. These rodents spend most of their life-time underground, and are less exposed to many of the environmental stimuli and challenges that are common to non-fossorial rodents. A prominent adaptation is their blindness, whic...
Article
To test the theory that sleep is a regional, use-dependent process, rats were subjected to unilateral sensory stimulation during waking. This was achieved by cutting the whiskers on one side, in order to reduce the sensory input to the contralateral cortex. The animals were kept awake for 6 h in an enriched environment to activate the cortex contra...
Chapter
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Sleep and waking are the two major functional states which in homeotherms can be unambiguously identified by both behavioral and electrophysiologic criteria. Sleep and waking are closely associated with rest and activity. The circadian rest-activity rhythm is present in organisms in which the usual criteria for sleep and waking cannot be applied (e...
Article
To test the theory that sleep is a regional, use-dependent process, rats were subjected to unilateral sensory stimulation during waking. This was achieved by cutting the whiskers on one side, in order to reduce the sensory input to the contralateral cortex. The animals were kept awake for 6 h in an enriched environment to activate the cortex contra...
Article
Full-text available
Running wheels are widely used in studies on biological rhythms. In mice wheel diameters have ranged from 11 cm to 23 cm. We provided mice with running wheels of two different sizes: 15 cm diameter and 11 cm diameter. The amount of running in the 12-h light:12-h dark condition and the endogenous period of wheel running in constant darkness was dete...
Article
Full-text available
Photoperiod influences the distribution of sleep and waking and electroencephalogram (EEG) power density in the Djungarian hamster. In an experimental procedure combining short photoperiod (SP) and low ambient temperature, the light-dark difference in the amount of sleep was decreased, and the changes in slow-wave activity (SWA) (mean EEG power den...
Article
Full-text available
Several recent results show that sleep and sleep regulation are not only global phenomena encompassing the entire brain, but have local features. It is well established that slow-wave activity [SWA; mean electroencephalographic (EEG) power density in the 0.75-4.0 Hz band] in non-rapid eye movement (NREM) sleep is a function of the prior history of...
Article
Despite the almost ubiquitous presence of sleep and the sleep stages nonREM and REM sleep in mammals and birds, the functions of sleep still remain elusive. Several promising approaches may s