scholarly journals Narcolepsy and the Dissociation of REM Sleep and Cataplexy through Ambient Temperature Manipulation

2021 ◽  
Author(s):  
Bianca Viberti ◽  
Lisa Branca ◽  
Simone Bellini ◽  
Claudio LA Bassetti ◽  
Antoine Adamantidis ◽  
...  
Keyword(s):  
Ambient Temperature ◽  
Rem Sleep ◽  
Activity Patterns ◽  
Active Phase ◽  
Nrem Sleep ◽  
Dark Phase ◽  
Inactive Phase ◽  
Temperature Manipulation ◽  
Unexpected Findings ◽  
Sleep Propensity

Narcolepsy is characterized by increased REM sleep propensity and cataplexy. Although narcolepsy is caused by the selective loss or dysfunction of hypocretin (Hcrt) neurons within the lateral hypothalamus (LH), mechanisms underlying REM sleep propensity and cataplexy remain to be elucidated. We have recently shown that wild type (WT) mice increase REM sleep expression when exposed to thermoneutral ambient temperature (Ta) warming during the light (inactive) phase. We hypothesized that the loss of Hcrt may lead to exaggerated responses with respect to increased REM sleep and cataplexy during Ta warming. To test this hypothesis, Hcrt-KO mice were implanted for chronic sleep recordings and housed in a temperature-controlled cabinet. Sleep-wake expression and both spontaneous cataplexy and food-elicited cataplexy were evaluated at constant Ta and during a Ta manipulation protocol. Here we show several unexpected findings. First, Hcrt-KO mice show opposite circadian patterns with respect to REM sleep responsiveness to thermoneutral Ta warming compared to WT mice. As previously demonstrated, WT mice increased REM sleep when Ta warming is presented during the inactive (light) phase, whereas Hcrt-KO showed a significant decrease in REM sleep expression. In contrast, Hcrt-KO mice increased REM sleep expression upon exposure to Ta warming when presented during the active (dark) phase, a circadian time when WT mice showed no significant changes in REM sleep as a function of Ta. Second, we found that REM sleep and cataplexy can be dissociated through Ta manipulation. Specifically, although Ta warming significantly increased REM sleep expression in Hcrt-KO mice during the active phase, cataplexy bout number and total cataplexy duration significantly decreased. In contrast, cataplexy expression was favoured during Ta cooling when REM sleep expression significantly decreased. Finally, video actigraphy and sleep-wake recordings in Hcrt-KO mice demonstrated that Ta manipulation did not significantly alter waking motor activity patterns or waking or NREM sleep durations. These data suggest that neural circuits gating REM sleep and cataplexy expression can be dissociated with Ta manipulation.

scholarly journals Nitric oxide synthase neurons in the preoptic hypothalamus are sleep-active and contribute to regulating NREM and REM sleep and lowering body temperature.

2021 ◽  
Author(s):  
Edward C Harding ◽  
Wei Ba ◽  
Reesha Zahir ◽  
Xiao Yu ◽  
Raquel Yustos ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Body Temperature ◽  
Nitric Oxide Synthase ◽  
Rem Sleep ◽  
Active Phase ◽  
Nrem Sleep ◽  
Dark Phase ◽  
Dark Light ◽  
Active Population ◽  
Oxide Synthase

When mice are exposed to external warmth, nitric oxide synthase (NOS1) neurons in the median and medial preoptic (MnPO/MPO) hypothalamus induce sleep and concomitant body cooling. However, how these neurons regulate baseline sleep and body temperature is unknown. Using calcium photometry, we show that NOS1 neurons in MnPO/MPO are predominantly NREM active. This is the first instance of a predominantly NREM-active population in the PO area, or to our knowledge, elsewhere in the brain. In addition to releasing nitric oxide, NOS1 neurons in MnPO/MPO can release GABA, glutamate and peptides. We expressed tetanus-toxin light-chain in MnPO/MPO NOS1 cells to reduce vesicular release of transmitters. This induced changes in sleep structure: over 24 hours, mice had less NREM sleep in their dark (active) phase, and more NREM sleep in their light (sleep) phase. REM sleep episodes in the dark phase were longer, and there were fewer REM transitions between other vigilance states. REM sleep had less theta power. Mice with synaptically-blocked MnPO/MPO NOS1 neurons were also warmer. In particular, mice were warmer than control mice at the dark-light transition (ZT0), as well as during the dark phase siesta (ZT16-20), where there is usually a body temperature dip. Also, at this siesta point of cooled body temperature, mice usually have more NREM, but mice with synaptically-blocked MnPO/MPO NOS1 cells showed reduced NREM sleep at this time. Overall, MnPO/MPO NOS1 neurons promote both NREM and REM sleep and contribute to chronically lowering body temperature, particularly at transitions where the mice normally enter NREM sleep.

scholarly journals Nitric Oxide Synthase Neurons in the Preoptic Hypothalamus Are NREM and REM Sleep-Active and Lower Body Temperature

2021 ◽  
Vol 15 ◽  
Author(s):  
Edward C. Harding ◽  
Wei Ba ◽  
Reesha Zahir ◽  
Xiao Yu ◽  
Raquel Yustos ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Body Temperature ◽  
Nitric Oxide Synthase ◽  
Rem Sleep ◽  
Active Phase ◽  
Nrem Sleep ◽  
Dark Phase ◽  
Dark Light ◽  
Body Cooling ◽  
Oxide Synthase

When mice are exposed to external warmth, nitric oxide synthase (NOS1) neurons in the median and medial preoptic (MnPO/MPO) hypothalamus induce sleep and concomitant body cooling. However, how these neurons regulate baseline sleep and body temperature is unknown. Using calcium photometry, we show that NOS1 neurons in MnPO/MPO are predominantly NREM and REM active, especially at the boundary of wake to NREM transitions, and in the later parts of REM bouts, with lower activity during wakefulness. In addition to releasing nitric oxide, NOS1 neurons in MnPO/MPO can release GABA, glutamate and peptides. We expressed tetanus-toxin light-chain in MnPO/MPO NOS1 cells to reduce vesicular release of transmitters. This induced changes in sleep structure: over 24 h, mice had less NREM sleep in their dark (active) phase, and more NREM sleep in their light (sleep) phase. REM sleep episodes in the dark phase were longer, and there were fewer REM transitions between other vigilance states. REM sleep had less theta power. Mice with synaptically blocked MnPO/MPO NOS1 neurons were also warmer than control mice at the dark-light transition (ZT0), as well as during the dark phase siesta (ZT16-20), where there is usually a body temperature dip. Also, at this siesta point of cooled body temperature, mice usually have more NREM, but mice with synaptically blocked MnPO/MPO NOS1 cells showed reduced NREM sleep at this time. Overall, MnPO/MPO NOS1 neurons promote both NREM and REM sleep and contribute to chronically lowering body temperature, particularly at transitions where the mice normally enter NREM sleep.

scholarly journals The European starling (Sturnus vulgaris) shows signs of NREM sleep homeostasis but has very little REM sleep and no REM sleep homeostasis

SLEEP ◽  
2019 ◽  
Vol 43 (6) ◽  
Author(s):  
Sjoerd J van Hasselt ◽  
Maria Rusche ◽  
Alexei L Vyssotski ◽  
Simon Verhulst ◽  
Niels C Rattenborg ◽  
...  
Keyword(s):  
Sleep Deprivation ◽  
Eye Movement ◽  
Rem Sleep ◽  
Spectral Power ◽  
Nrem Sleep ◽  
Sleep Time ◽  
European Starling ◽  
Dark Phase ◽  
Rapid Eye Movement ◽  
Sleep Homeostasis

Abstract Most of our knowledge about the regulation and function of sleep is based on studies in a restricted number of mammalian species, particularly nocturnal rodents. Hence, there is still much to learn from comparative studies in other species. Birds are interesting because they appear to share key aspects of sleep with mammals, including the presence of two different forms of sleep, i.e. non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. We examined sleep architecture and sleep homeostasis in the European starling, using miniature dataloggers for electroencephalogram (EEG) recordings. Under controlled laboratory conditions with a 12:12 h light–dark cycle, the birds displayed a pronounced daily rhythm in sleep and wakefulness with most sleep occurring during the dark phase. Sleep mainly consisted of NREM sleep. In fact, the amount of REM sleep added up to only 1~2% of total sleep time. Animals were subjected to 4 or 8 h sleep deprivation to assess sleep homeostatic responses. Sleep deprivation induced changes in subsequent NREM sleep EEG spectral qualities for several hours, with increased spectral power from 1.17 Hz up to at least 25 Hz. In contrast, power below 1.17 Hz was decreased after sleep deprivation. Sleep deprivation also resulted in a small compensatory increase in NREM sleep time the next day. Changes in EEG spectral power and sleep time were largely similar after 4 and 8 h sleep deprivation. REM sleep was not noticeably compensated after sleep deprivation. In conclusion, starlings display signs of NREM sleep homeostasis but the results do not support the notion of important REM sleep functions.

scholarly journals Time matters: pathological effects of repeated psychosocial stress during the active, but not inactive, phase of male mice

2012 ◽  
Vol 215 (3) ◽  
pp. 425-437 ◽  
Author(s):  
Manuela S Bartlang ◽  
Inga D Neumann ◽  
David A Slattery ◽  
Nicole Uschold-Schmidt ◽  
Dominik Kraus ◽  
...  
Keyword(s):  
Social Preference ◽  
Active Phase ◽  
Time Of Day ◽  
Dark Phase ◽  
Light Phase ◽  
Immunological Parameters ◽  
Repeated Restraint Stress ◽  
Inactive Phase ◽  
Home Cage Activity

Recent findings in rats indicated that the physiological consequences of repeated restraint stress are dependent on the time of day of stressor exposure. To investigate whether this is also true for clinically more relevant psychosocial stressors and whether repeated stressor exposure during the light phase or dark phase is more detrimental for an organism, we exposed male C57BL/6 mice to social defeat (SD) across 19 days either in the light phase between Zeitgeber time (ZT)1 and ZT3 (SDL mice) or in the dark phase between ZT13 and ZT15 (SDD mice). While SDL mice showed a prolonged increase in adrenal weight and an attenuated adrenal responsiveness to ACTHin vitroafter stressor termination, SDD mice showed reduced dark phase home-cage activity on observation days 7, 14, and 20, flattening of the diurnal corticosterone rhythm, lack of social preference, and higherin vitroIFNγ secretion from mesenteric lymph node cells on day 20/21. Furthermore, the colitis-aggravating effect of SD was more pronounced in SDD than SDL mice following dextran sulfate sodium treatment. In conclusion, the present findings demonstrate that repeated SD effects on behavior, physiology, and immunology strongly depend on the time of day of stressor exposure. Whereas physiological parameters were more affected by SD during the light/inactive phase of mice, behavioral and immunological parameters were more affected by SD during the dark phase. Our results imply that repeated daily SD exposure has a more negative outcome when applied during the dark/active phase. By contrast, the minor physiological changes seen in SDL mice might represent beneficial adaptations preventing the formation of those maladaptive consequences.

scholarly journals Estradiol modulates recovery of REM sleep in a time-of-day-dependent manner

2013 ◽  
Vol 305 (3) ◽  
pp. R271-R280 ◽  
Author(s):  
Michael D. Schwartz ◽  
Jessica A. Mong
Keyword(s):  
Rem Sleep ◽  
Nrem Sleep ◽  
Estradiol Benzoate ◽  
Time Of Day ◽  
Female Rats ◽  
Dark Phase ◽  
Dependent Manner ◽  
Light Phase ◽  
Sleep Complaints ◽  
Hormonal Milieu

Ovarian hormones are thought to modulate sleep and fluctuations in the hormonal milieu are coincident with sleep complaints in women. In female rats, estradiol increases waking and suppresses sleep. In this study, we asked whether this effect is mediated via circadian or homeostatic regulatory mechanisms. Ovariectomized female rats received daily injections of estradiol benzoate (EB) or sesame oil that mimicked the rapid increase and subsequent decline of circulating estradiol at proestrus. In one experiment, animals were sleep deprived for 6 h starting at lights-on, so that recovery began in the mid-light phase; in the second experiment, animals were sleep deprived starting in the mid-light phase, so that recovery began at lights-off. EB suppressed baseline rapid eye movement (REM) and non-REM (NREM) sleep and increased waking in the dark phase. In both experiments, EB enhanced REM recovery in the light phase while suppressing it in the dark compared with oil; this effect was most pronounced in the first 6 h of recovery. By contrast, NREM recovery was largely unaffected by EB. In summary, EB enhanced waking and suppressed sleep, particularly REM sleep, in the dark under baseline and recovery conditions. These strong temporally dependent effects suggest that EB consolidates circadian sleep-wake rhythms in female rats.

Altered sleep and behavioral activity phenotypes in PER3-deficient mice

2011 ◽  
Vol 301 (6) ◽  
pp. R1821-R1830 ◽  
Author(s):  
Sibah Hasan ◽  
Daan R. van der Veen ◽  
Raphaelle Winsky-Sommerer ◽  
Derk-Jan Dijk ◽  
Simon N. Archer
Keyword(s):  
Rem Sleep ◽  
Wheel Running ◽  
Nrem Sleep ◽  
Light Period ◽  
Behavioral Activity ◽  
Dark Phase ◽  
Running Activity ◽  
Sleep Homeostasis ◽  
Wheel Running Activity ◽  
Delta Activity

Sleep homeostasis and circadian rhythmicity interact to determine the timing of behavioral activity. Circadian clock genes contribute to circadian rhythmicity centrally and in the periphery, but some also have roles within sleep regulation. The clock gene Period3 ( Per3) has a redundant function within the circadian system and is associated with sleep homeostasis in humans. This study investigated the role of PER3 in sleep/wake activity and sleep homeostasis in mice by recording wheel-running activity under baseline conditions in wild-type (WT; n = 54) and in PER3-deficient ( Per3−/−; n = 53) mice, as well as EEG-assessed sleep before and after 6 h of sleep deprivation in WT ( n = 7) and Per3−/− ( n = 8) mice. Whereas total activity and vigilance states did not differ between the genotypes, the temporal distribution of wheel-running activity, vigilance states, and EEG delta activity was affected by genotype. In Per3−/− mice, running wheel activity was increased, and REM sleep and NREM sleep were reduced in the middle of the dark phase, and delta activity was enhanced at the end of the dark phase. At the beginning of the baseline light period, there was less wakefulness and more REM and NREM sleep in Per3−/− mice. Per3−/− mice spent less time in wakefulness and more time in NREM sleep in the light period immediately after sleep deprivation, and REM sleep accumulated more slowly during the recovery dark phase. These data confirm a role for PER3 in sleep-wake timing and sleep homeostasis.

REM-sleep timing is controlled homeostatically by accumulation of REM-sleep propensity in non-REM sleep

1994 ◽  
Vol 266 (6) ◽  
pp. R1992-R2000 ◽  
Author(s):  
J. H. Benington ◽  
H. C. Heller
Keyword(s):  
Rem Sleep ◽  
Sleep Onset ◽  
Nrem Sleep ◽  
Sleep Episode ◽  
Sleep Timing ◽  
Sleep Maintenance ◽  
Oscillatory Mechanism ◽  
Episode Duration ◽  
Full Day ◽  
Sleep Propensity

Sleep structure in the rat was characterized during uninterrupted full-day recordings using an analytic procedure that identifies rapid eye movement (REM) sleep episodes based on REM-sleep-onset electroencephalograph phenomena, hence independently of REM-sleep duration. The data were used to determine whether REM-sleep timing is controlled homeostatically or by an oscillatory mechanism. The findings and conclusions are that 1) non-REM (NREM) sleep episode duration is positively correlated with prior REM-sleep episode duration, suggesting that REM-sleep expression is permissive of NREM sleep; 2) mean NREM-sleep episode duration decreases after repeated brief REM-sleep episodes (< 30 s), also suggesting that discharge of REM-sleep propensity is essential for NREM-sleep expression; 3) REM-sleep episode duration is independent of prior sleep history, suggesting that REM-sleep maintenance is controlled by factors other than accumulated REM-sleep propensity; 4) brief REM-sleep episodes occur progressively more frequently over the course of the NREM-sleep interval between sustained REM-sleep episodes (> 30 s), suggesting that REM-sleep propensity increases progressively within episodes of NREM sleep; and 5) the diurnal cycle of REM-sleep expression primarily reflects modulation in the efficiency of REM-sleep maintenance. These findings support the hypothesis that REM-sleep timing is controlled by accumulation of REM-sleep propensity during NREM sleep.

scholarly journals A probabilistic model for the ultradian timing of REM sleep in mice

2021 ◽  
Vol 17 (8) ◽  
pp. e1009316
Author(s):  
Sung-Ho Park ◽  
Justin Baik ◽  
Jiso Hong ◽  
Hanna Antila ◽  
Benjamin Kurland ◽  
...  
Keyword(s):  
Sleep Duration ◽  
Rem Sleep ◽  
Salient Feature ◽  
Nrem Sleep ◽  
Sleep Stages ◽  
Dark Phase ◽  
Sleep Episode ◽  
Health And Disease ◽  
Flexible Framework ◽  
Data Driven Modeling

A salient feature of mammalian sleep is the alternation between rapid eye movement (REM) and non-REM (NREM) sleep. However, how these two sleep stages influence each other and thereby regulate the timing of REM sleep episodes is still largely unresolved. Here, we developed a statistical model that specifies the relationship between REM and subsequent NREM sleep to quantify how REM sleep affects the following NREM sleep duration and its electrophysiological features in mice. We show that a lognormal mixture model well describes how the preceding REM sleep duration influences the amount of NREM sleep till the next REM sleep episode. The model supports the existence of two different types of sleep cycles: Short cycles form closely interspaced sequences of REM sleep episodes, whereas during long cycles, REM sleep is first followed by an interval of NREM sleep during which transitions to REM sleep are extremely unlikely. This refractory period is characterized by low power in the theta and sigma range of the electroencephalogram (EEG), low spindle rate and frequent microarousals, and its duration proportionally increases with the preceding REM sleep duration. Using our model, we estimated the propensity for REM sleep at the transition from NREM to REM sleep and found that entering REM sleep with higher propensity resulted in longer REM sleep episodes with reduced EEG power. Compared with the light phase, the buildup of REM sleep propensity was slower during the dark phase. Our data-driven modeling approach uncovered basic principles underlying the timing and duration of REM sleep episodes in mice and provides a flexible framework to describe the ultradian regulation of REM sleep in health and disease.

Persistence of sleep-temperature coupling after suprachiasmatic nuclei lesions in rats

2005 ◽  
Vol 289 (3) ◽  
pp. R827-R838 ◽  
Author(s):  
F. C. Baker ◽  
C. Angara ◽  
R. Szymusiak ◽  
D. McGinty
Keyword(s):  
Ambient Temperature ◽  
Rem Sleep ◽  
Cross Correlation ◽  
Brain Temperature ◽  
Nrem Sleep ◽  
Wave Activity ◽  
Ultradian Rhythms ◽  
Suprachiasmatic Nuclei ◽  
Slow Decline ◽  
Cross Correlation Analysis

The suprachiasmatic nucleus (SCN) regulates the circadian rhythms of body temperature (Tb) and vigilance states in mammals. We studied rats in which circadian rhythmicity was abolished after SCN lesions (SCNx rats) to investigate the association between the ultradian rhythms of sleep-wake states and brain temperature (Tbr), which are exposed after lesions. Ultradian rhythms of Tbr (mean period: 3.6 h) and sleep were closely associated in SCNx rats. Within each ultradian cycle, nonrapid eye movement (NREM) sleep was initiated 5 ± 1 min after Tbr peaks, after which temperature continued a slow decline (0.02 ± 0.006°C/min) until it reached a minimum. Sleep and slow wave activity (SWA), an index of sleep intensity, were associated with declining temperature. Cross-correlation analysis revealed that the rhythm of Tbr preceded that of SWA by 2–10 min. We also investigated the thermoregulatory and sleep-wake responses of SCNx rats and controls to mild ambient cooling (18°C) and warming (30°C) over 24-h periods. SCNx rats and controls responded similarly to changes in ambient temperature. Cooling decreased REM sleep and increased wake. Warming increased Tbr, blunted the amplitude of ultradian Tbr rhythms, and increased the number of transitions into NREM sleep. SCNx rats and controls had similar percentages of NREM sleep, REM sleep, and wake, as well as the same average Tb within each 24-h period. Our results suggest that, in rats, the SCN modulates the timing but not the amount of sleep or the homeostatic control of sleep-wake states or Tb during deviations in ambient temperature.

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.

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