scholarly journals The molecular clockwork of the suprachiasmatic nucleus is sufficient to co-ordinate phasing and stabilisation of sleep-wake cycles and enhance memory deficits in a clockless mouse

2021 ◽  
Author(s):  
Elizabeth S. Maywood ◽  
Johanna E. Chesham ◽  
Raphaelle Winsky-Sommerer ◽  
Michael H. Hastings
Keyword(s):  
Circadian Clock ◽  
Suprachiasmatic Nucleus ◽  
Recovery Period ◽  
Nrem Sleep ◽  
Genetic Complementation ◽  
Poor Sleep ◽  
Delta Power ◽  
Circadian Control ◽  
Sleep Consolidation ◽  
The Brain

AbstractThe timing and quality of sleep-wake cycles are regulated by interacting circadian and homeostatic mechanisms. Although the suprachiasmatic nucleus (SCN) is the principal circadian clock, local clocks are active across the brain and the respective sleep-regulatory roles of SCN and extra-SCN clocks are unclear. To determine the specific contribution(s) of the SCN, we used virally mediated genetic complementation, expressing Cryptochrome1 (Cry1) to restore circadian molecular competence to the SCN of globally clockless Cry1/Cry2-null mice. Under free-running conditions, the rest/activity behaviour of Cry1/Cry2-null controls which received EGFP (SCNCon) was arrhythmic, whereas Cry1-complemented mice (SCNCry1) had circadian behaviour comparable to that of Cry1,2-competent wild-types (WT). In SCNCon mice, sleep-wakefulness, assessed by electroencephalography/electromyography, also lacked circadian organisation. In SCNCry1 mice, however, it was comparable to WT, with consolidated vigilance states (wake, REM and NREM sleep) and rhythms in NREMS delta power and expression of REMS within total sleep. Wakefulness in SCNCon mice was more fragmented than in WT, with more wake-NREMS-wake transitions. This disruption was corrected in SCNCry1 mice. Following sleep deprivation, all mice showed an initial homeostatic increase in NREMS delta power. The SCNCon mice, however, had reduced, non-consolidated NREMS during the inactive phase of the recovery period. In contrast, the dynamics of homeostatic responses in the SCNCry1 mice were equivalent to WT. Finally, SCNCon mice exhibited poor sleep-dependent memory but this was corrected in SCNCry1mice. Therefore, the SCN clock is sufficient for circadian control of sleep-wake, facilitating initiation and maintenance of wake, promoting sleep consolidation, homeostatic dynamics, and sleep-dependent memory.Significance statementThe circadian timing system regulates sleep-wake cycles. The hypothalamic suprachiasmatic nucleus (SCN) is the principal circadian clock, but local clocks are also active across the brain and the respective roles of SCN and local clocks in regulating sleep are unclear. To determine, explicitly, the contribution of the SCN, we used virally mediated genetic complementation to restore SCN molecular circadian functions in otherwise genetically clockless mice. This initiated circadian activity-rest cycles, accompanied by circadian sleep-wake cycles, circadian patterning to the intensity of NREM sleep and circadian control of REM sleep as a proportion of total sleep. Consolidation of sleep-wake established normal dynamics of sleep homeostasis and enhanced sleep-dependent memory. Thus, the SCN is the principal and sufficient circadian regulator of sleep-wake.

scholarly journals Light sets the brain’s daily clock by regional quickening and slowing of the molecular clockworks at dawn and dusk

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Suil Kim ◽  
Douglas G McMahon
Keyword(s):  
Neural Network ◽  
Circadian Clock ◽  
Suprachiasmatic Nucleus ◽  
Clock Gene ◽  
Ex Vivo ◽  
Period Effects ◽  
Free Running ◽  
And Behavior ◽  
The Brain ◽  
Light Input

How daily clocks in the brain are set by light to local environmental time and encode the seasons is not fully understood. The suprachiasmatic nucleus (SCN) is a central circadian clock in mammals that orchestrates physiology and behavior in tune with daily and seasonal light cycles. Here, we have found that optogenetically simulated light input to explanted mouse SCN changes the waveform of the molecular clockworks from sinusoids in free-running conditions to highly asymmetrical shapes with accelerated synthetic (rising) phases and extended degradative (falling) phases marking clock advances and delays at simulated dawn and dusk. Daily waveform changes arise under ex vivo entrainment to simulated winter and summer photoperiods, and to non-24 hr periods. Ex vivo SCN imaging further suggests that acute waveform shifts are greatest in the ventrolateral SCN, while period effects are greatest in the dorsomedial SCN. Thus, circadian entrainment is encoded by SCN clock gene waveform changes that arise from spatiotemporally distinct intrinsic responses within the SCN neural network.

Homeostatic regulation of NREM sleep, but not REM sleep, in Australian magpies

SLEEP ◽  
2021 ◽  
Author(s):  
Robin D Johnsson ◽  
Farley Connelly ◽  
Alexei L Vyssotski ◽  
Timothy C Roth ◽  
John A Lesku
Keyword(s):  
Rem Sleep ◽  
Recovery Period ◽  
Nrem Sleep ◽  
Night Time ◽  
Apparent Absence ◽  
Recovery Sleep ◽  
Sleep Homeostasis ◽  
Baseline Recording ◽  
Sleep Consolidation ◽  
Multiple Species

Abstract Study Objectives We explore NREM and REM sleep homeostasis in Australian magpies (Cracticus tibicen tyrannica). We predicted that magpies would recover lost sleep by spending more time in NREM and REM sleep, and by engaging in more intense NREM sleep as indicated by increased slow-wave activity (SWA). Methods Continuous 72-h recordings of EEG, EMG and tri-axial accelerometry, along with EEG spectral analyses, were performed on wild-caught Australian magpies housed in indoor aviaries. Australian magpies were subjected to two protocols of night-time sleep deprivation: full 12-h night (n = 8) and first 6-h half of the night (n = 5), which were preceded by a 36-h baseline recording and followed by a 24-h recovery period. Results Australian magpies recovered lost NREM sleep by sleeping more, with increased NREM sleep consolidation, and increased SWA during recovery sleep. Following 12-h of night-time sleep loss, magpies also showed reduced SWA the following night after napping more during the recovery day. Surprisingly, the magpies did not recover any lost REM sleep. Conclusions Only NREM sleep is homeostatically regulated in Australian magpies with the level of SWA reflecting prior sleep/wake history. The significance of emerging patterns on the apparent absence of REM sleep homeostasis, now observed in multiple species, remains unclear.

scholarly journals Circadian Chimeric Mice Reveal an Interplay Between the Suprachiasmatic Nucleus and Local Brain Clocks in the Control of Sleep and Memory

2021 ◽  
Vol 15 ◽  
Author(s):  
Elizabeth Susan Maywood ◽  
Johanna Elizabeth Chesham ◽  
Raphaelle Winsky-Sommerer ◽  
Nicola Jane Smyllie ◽  
Michael Harvey Hastings
Keyword(s):  
Suprachiasmatic Nucleus ◽  
Ex Vivo ◽  
Circadian Clocks ◽  
Chimeric Mice ◽  
Sleep Regulation ◽  
Circadian Control ◽  
A Cell ◽  
The Brain ◽  
Local Brain

Sleep is regulated by circadian and homeostatic processes. Whereas the suprachiasmatic nucleus (SCN) is viewed as the principal mediator of circadian control, the contributions of sub-ordinate local circadian clocks distributed across the brain are unknown. To test whether the SCN and local brain clocks interact to regulate sleep, we used intersectional genetics to create temporally chimeric CK1ε Tau mice, in which dopamine 1a receptor (Drd1a)-expressing cells, a powerful pacemaking sub-population of the SCN, had a cell-autonomous circadian period of 24 h whereas the rest of the SCN and the brain had intrinsic periods of 20 h. We compared these mice with non-chimeric 24 h wild-types (WT) and 20 h CK1ε Tau mutants. The periods of the SCN ex vivo and the in vivo circadian behavior of chimeric mice were 24 h, as with WT, whereas other tissues in the chimeras had ex vivo periods of 20 h, as did all tissues from Tau mice. Nevertheless, the chimeric SCN imposed its 24 h period on the circadian patterning of sleep. When compared to 24 h WT and 20 h Tau mice, however, the sleep/wake cycle of chimeric mice under free-running conditions was disrupted, with more fragmented sleep and an increased number of short NREMS and REMS episodes. Even though the chimeras could entrain to 20 h light:dark cycles, the onset of activity and wakefulness was delayed, suggesting that SCN Drd1a-Cre cells regulate the sleep/wake transition. Chimeric mice also displayed a blunted homeostatic response to 6 h sleep deprivation (SD) with an impaired ability to recover lost sleep. Furthermore, sleep-dependent memory was compromised in chimeras, which performed significantly worse than 24 h WT and 20 h Tau mice. These results demonstrate a central role for the circadian clocks of SCN Drd1a cells in circadian sleep regulation, but they also indicate a role for extra-SCN clocks. In circumstances where the SCN and sub-ordinate local clocks are temporally mis-aligned, the SCN can maintain overall circadian control, but sleep consolidation and recovery from SD are compromised. The importance of temporal alignment between SCN and extra-SCN clocks for maintaining vigilance state, restorative sleep and memory may have relevance to circadian misalignment in humans, with environmental (e.g., shift work) causes.

scholarly journals Multitissue Circadian Expression of RatperiodHomolog (rPer2) mRNA Is Governed by the Mammalian Circadian Clock, the Suprachiasmatic Nucleus in the Brain

1998 ◽  
Vol 273 (42) ◽  
pp. 27039-27042 ◽  
Author(s):  
Katsuhiko Sakamoto ◽  
Takahiro Nagase ◽  
Hiromi Fukui ◽  
Kazumasa Horikawa ◽  
Tetsuya Okada ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Suprachiasmatic Nucleus ◽  
Circadian Expression ◽  
The Brain

scholarly journals Toward asleep DBS: cortico-basal ganglia spectral and coherence activity during interleaved propofol/ketamine sedation mimics NREM/REM sleep activity

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Jing Guang ◽  
Halen Baker ◽  
Orilia Ben-Yishay Nizri ◽  
Shimon Firman ◽  
Uri Werner-Reiss ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Rem Sleep ◽  
Standard Procedure ◽  
Low Frequency ◽  
Nrem Sleep ◽  
Sleep Cycle ◽  
Advanced Parkinson’S Disease ◽  
Low Frequency Power ◽  
The Brain ◽  
Frequency Power

AbstractDeep brain stimulation (DBS) is currently a standard procedure for advanced Parkinson’s disease. Many centers employ awake physiological navigation and stimulation assessment to optimize DBS localization and outcome. To enable DBS under sedation, asleep DBS, we characterized the cortico-basal ganglia neuronal network of two nonhuman primates under propofol, ketamine, and interleaved propofol-ketamine (IPK) sedation. Further, we compared these sedation states in the healthy and Parkinsonian condition to those of healthy sleep. Ketamine increases high-frequency power and synchronization while propofol increases low-frequency power and synchronization in polysomnography and neuronal activity recordings. Thus, ketamine does not mask the low-frequency oscillations used for physiological navigation toward the basal ganglia DBS targets. The brain spectral state under ketamine and propofol mimicked rapid eye movement (REM) and Non-REM (NREM) sleep activity, respectively, and the IPK protocol resembles the NREM-REM sleep cycle. These promising results are a meaningful step toward asleep DBS with nondistorted physiological navigation.

scholarly journals 0327 NREM Sleep EEG in Typically Developing and Drug-Naïve ADHD Adolescents: Data from a Longitudinal Study

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A124-A124
Author(s):  
T Basishvili ◽  
M Eliozishvili ◽  
T Oniani ◽  
T Tchintcharauli ◽  
I Sakhelashvili ◽  
...  
Keyword(s):  
Longitudinal Study ◽  
Nrem Sleep ◽  
Sleep Eeg ◽  
Brain Maturation ◽  
Adhd Group ◽  
Typically Developing ◽  
Eeg Activity ◽  
Theta Power ◽  
Delta Power ◽  
Drug Naïve

Abstract Introduction Structural MRI studies suggest delayed brain maturation in children with attention deficit hyperactivity disorder (ADHD). The steep adolescent decline in sleep slow wave EEG activity provides an opportunity to investigate brain electrophysiological evidence for this maturational delay. Most ADHD sleep EEG studies have been cross-sectional. Here we present data from an ongoing longitudinal study of the maturational trajectories of sleep EEG in drug-naïve ADHD and typically developing adolescents. Methods Nine children diagnosed with ADHD (combined subtype, DSM-V criteria, mean age 12.39±0.61 years), and nine typically developing controls (12.07±0.35 years) were recruited. Subjects underwent an adaptation night and all night polysomnography twice yearly at the Laboratory. Sleep EEG was analyzed using fast Fourier transform. NREM delta and theta EEG activity were compared across first two recordings. Results Group effects (ADHD vs. control) on all night delta and theta energy, and delta power were not significant (p>0.2 for all). All night theta power was lower (p=0.035) for the ADHD group, and all night NREM sleep duration trended (p=0.060) toward being lower for the ADHD group. Controlling for sleep duration differences by examining only the first 5 h of NREM sleep showed no group effect on delta power (p=0.77) and a trend toward lower theta power (p=0.057) for the ADHD group. Conclusion At age 12 to 13 years, NREM sleep delta EEG did not differ between ADHD and control subjects. Theta power, which declines at a younger age than delta, was lower in control subjects. The two recordings thus far differ only by 6 months. The entire study will provide 5 semiannual recordings and allow us to determine if the higher theta power in the ADHD group will hold and if delta power will be greater as well, and thus provide electrophysiological support for the delayed brain maturation suggested by MRI findings. Support Shota Rustaveli National Science Foundation Grant FR17_94; Subjects Recruitment Support - Mental Health Service in Tbilisi “Kamara”.

scholarly journals Intracellular pH in the Brain following Transient Ischemia

1983 ◽  
Vol 3 (1) ◽  
pp. 109-114 ◽  
Author(s):  
Hideo Mabe ◽  
Photjanee Blomqvist ◽  
Bo K. Siesjö
Keyword(s):  
Creatine Kinase ◽  
Lactic Acid ◽  
Intracellular Ph ◽  
Adenine Nucleotides ◽  
Recovery Period ◽  
Transient Ischemia ◽  
Vessel Occlusion ◽  
Atp Production ◽  
Creatine Kinase Reaction ◽  
The Brain

The objective of the present study was to discover whether or not intracellular alkalosis develops in the brain in the recovery period following transient ischemia. Forebrain ischemia of 15-min duration was induced by four-vessel occlusion in rats, with recovery periods of 15, 60, and 180 min. Intracellular pH was derived both by the HCO3−–H2CO3 method and from the creatine kinase equilibrium. The ischemia was associated with energy failure and marked accumulation of lactic acid in the cerebral cortex. Recirculation brought about rapid rephosphorylation of adenine nucleotides and gradual normalization of lactic acid levels. After 15 min of recovery, the HCO3−–H2CO3 method indicated persisting acidosis, but the creatine kinase reaction did not. After 60 min, a shift of pH in the alkaline direction was demonstrated in both methods. This alkalosis had disappeared after 3 h of recovery. It is concluded that resumption of ATP production after ischemia is followed by a rapid rise in intracellular pH, which transiently increases above normal.

scholarly journals Cryptochromes regulate IGF-1 production and signaling through control of JAK2-dependent STAT5B phosphorylation

2017 ◽  
Vol 28 (6) ◽  
pp. 834-842 ◽  
Author(s):  
Amol Chaudhari ◽  
Richa Gupta ◽  
Sonal Patel ◽  
Nikkhil Velingkaar ◽  
Roman Kondratov
Keyword(s):  
Circadian Rhythms ◽  
Circadian Clock ◽  
Skeletal Muscles ◽  
Cancer Metabolism ◽  
Reduced Body ◽  
Circadian Control ◽  
Cell Growth And Proliferation ◽  
Deficient Mice ◽  
Igf Signaling

Insulin-like growth factor (IGF) signaling plays an important role in cell growth and proliferation and is implicated in regulation of cancer, metabolism, and aging. Here we report that IGF-1 level in blood and IGF-1 signaling demonstrates circadian rhythms. Circadian control occurs through cryptochromes (CRYs)—transcriptional repressors and components of the circadian clock. IGF-1 rhythms are disrupted in Cry-deficient mice, and IGF-1 level is reduced by 80% in these mice, which leads to reduced IGF signaling. In agreement, Cry-deficient mice have reduced body (∼30% reduction) and organ size. Down-regulation of IGF-1 upon Cry deficiency correlates with reduced Igf-1 mRNA expression in the liver and skeletal muscles. Igf-1 transcription is regulated through growth hormone–induced, JAK2 kinase–mediated phosphorylation of transcriptional factor STAT5B. The phosphorylation of STAT5B on the JAK2-dependent Y699 site is significantly reduced in the liver and skeletal muscles of Cry-deficient mice. At the same time, phosphorylation of JAK2 kinase was not reduced upon Cry deficiency, which places CRY activity downstream from JAK2. Thus CRYs link the circadian clock and JAK-STAT signaling through control of STAT5B phosphorylation, which provides the mechanism for circadian rhythms in IGF signaling in vivo.

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