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

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.

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

SLEEP ◽

10.1093/sleep/zsz311 ◽

2019 ◽

Vol 43 (6) ◽

Cited By ~ 4

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.

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Loss of endothelin B receptor function impairs sodium excretion in a time- and sex-dependent manner

AJP Renal Physiology ◽

10.1152/ajprenal.00103.2016 ◽

2016 ◽

Vol 311 (5) ◽

pp. F991-F998 ◽

Cited By ~ 19

Author(s):

Jermaine G. Johnston ◽

Joshua S. Speed ◽

Chunhua Jin ◽

David M. Pollock

Keyword(s):

Sodium Excretion ◽

Receptor Activation ◽

Time Of Day ◽

Female Rats ◽

Sodium Balance ◽

Dependent Manner ◽

Endothelin B Receptor ◽

Salt Load ◽

Endothelin B ◽

Nacl Load

Recent studies suggested a direct link between circadian rhythms and regulation of sodium excretion. Endothelin-1 (ET-1) regulates sodium balance by promoting natriuresis through the endothelin B receptor (ETB) in response to increased salt in the diet, but the effect that the time of day has on this natriuretic response is not known. Therefore, this study was designed to test the hypothesis that ETB receptor activation contributes to the diurnal control of sodium excretion and that sex differences contribute to this control as well. Twelve-hour urine collections were used to measure sodium excretion. On day 3 of the experiment, a NaCl load (900 μeq) was given by oral gavage either at Zeitgeber time [ZT] 0 (inactive period) or ZT12 (active period) to examine the natriuretic response to the acute salt load. Male and female ETB-deficient (ETB def) rats showed an impaired natriuretic response to a salt load at ZT0 compared with their respective transgenic controls (Tg cont). Male ETB def rats showed a delayed natriuretic response to a salt load given at ZT12 compared with male Tg cont, a contrast to the prompt response shown by female ETB def rats. Treatment with ABT-627, an ETA receptor antagonist, improved the natriuretic response seen within the first 12 h of a ZT0 salt load in both sexes. These findings demonstrate that diurnal excretion of an acute salt load 1) requires ET-1 and the ETB receptor, 2) is more evident in male vs. female rats, and 3) is opposed by the ETA receptor.

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

Journal of Endocrinology ◽

10.1530/joe-12-0267 ◽

2012 ◽

Vol 215 (3) ◽

pp. 425-437 ◽

Cited By ~ 30

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.

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State-dependent pontine ensemble dynamics and interactions with cortex across sleep states

10.1101/752683 ◽

2019 ◽

Cited By ~ 1

Author(s):

Tomomi Tsunematsu ◽

Amisha A Patel ◽

Arno Onken ◽

Shuzo Sakata

Keyword(s):

Rem Sleep ◽

Hippocampal Neurons ◽

Specific Activity ◽

Nrem Sleep ◽

Dependent Manner ◽

Sleep Regulation ◽

Population Activity ◽

P Waves ◽

State Dependent ◽

Global Coordination

AbstractThe pontine nuclei play a crucial role in sleep-wake regulation. However, pontine ensemble dynamics underlying sleep regulation remain poorly understood. By monitoring population activity in multiple pontine and adjacent brainstem areas, here we show slow, state-predictive pontine ensemble dynamics and state-dependent interactions between the pons and the cortex in mice. On a timescale of seconds to minutes, pontine populations exhibit diverse firing across vigilance states, with some of these dynamics being attributed to cell type-specific activity. Pontine population activity can predict pupil dilation and vigilance states: pontine neurons exhibit longer predictable power compared with hippocampal neurons. On a timescale of sub-seconds, pontine waves (P-waves) are observed as synchronous firing of pontine neurons primarily during rapid eye movement (REM) sleep, but also during non-REM (NREM) sleep. Crucially, P-waves functionally interact with cortical activity in a state-dependent manner: during NREM sleep, hippocampal sharp wave-ripples (SWRs) precede P-waves. On the other hand, P-waves during REM sleep are phase-locked with ongoing hippocampal theta oscillations and are followed by burst firing in a subset of hippocampal neurons. Thus, the directionality of functional interactions between the hippocampus and pons changes depending on sleep states. This state-dependent global coordination between pontine and cortical regions implicates distinct functional roles of sleep.

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Fluoxetine Mimics the Anorectic Action of Estrogen and Its Regulation of Circadian Feeding in Ovariectomized Female Rats

Nutrients ◽

10.3390/nu12030849 ◽

2020 ◽

Vol 12 (3) ◽

pp. 849 ◽

Cited By ~ 1

Author(s):

Yuri Nishimura ◽

Kaori Mabuchi ◽

Natsumi Omura ◽

Ayako Igarashi ◽

Megumi Miura ◽

...

Keyword(s):

Food Intake ◽

Selective Serotonin Reuptake Inhibitors ◽

Body Weight Gain ◽

Treated Group ◽

Female Rats ◽

Ovariectomized Rats ◽

Dark Phase ◽

Light Phase ◽

Serotonergic Neurons ◽

Fos Expression

Our previous study demonstrated that chronic estrogen replacement in ovariectomized rats reduces food intake and augments c-Fos expression in the suprachiasmatic nucleus (SCN), specifically during the light phase. Here, we hypothesized that serotonergic neurons in the central nervous system (CNS), which have anorectic action and play a role in regulating circadian rhythm, mediate the light phase-specific anorectic action of estrogen, and that selective serotonin reuptake inhibitors (SSRIs) mimic the hypophagic action of estrogen. Female Wistar rats were ovariectomized and treated with estradiol (E2) or cholesterol by subcutaneously implanting a silicon capsule containing E2 or cholesterol. Then, half of the cholesterol-treated rats were injected with the SSRI fluoxetine (5 mg/kg) (FLX group), while the remaining rats in the cholesterol-treated group (CON group) and all those in the E2 group were injected with saline subcutaneously twice daily at the onsets of the light and dark phases. Both E2 and FLX reduced food intake during the light phase but not the dark phase, and reduced body weight gain. In addition, both E2 and FLX augmented the c-Fos expression in the SCN, specifically during the light phase. These data indicate that FLX exerts estrogen-like antiobesity and hypophagic actions by modifying circadian feeding patterns, and suggest that estrogen regulates circadian feeding rhythm via serotonergic neurons in the CNS.

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0156 Activation of Glutamatergic PPT Neurons and Their Projections Promotes Arousal, and Distinct Wake Behaviors

SLEEP ◽

10.1093/sleep/zsaa056.154 ◽

2020 ◽

Vol 43 (Supplement_1) ◽

pp. A61-A62

Author(s):

D Kroeger ◽

J A Thundercliffe ◽

A Phung ◽

C Geraci ◽

R DeLuca ◽

...

Keyword(s):

Substantia Nigra ◽

Optical Fibers ◽

Lateral Hypothalamus ◽

Rem Sleep ◽

Basal Forebrain ◽

Viral Vector ◽

Nrem Sleep ◽

Blue Laser ◽

Dependent Manner ◽

Glutamatergic Neurons

Abstract Introduction The pedunculopontine tegmental (PPT) region in the brainstem is crucial for the regulation of sleep/wake states. We recently showed that chemogenetic activation of glutamatergic PPT neurons promotes wakefulness for several hours. Here we used optogenetic activation of these neurons to further investigate the mechanisms and pathways through which PPT glutamatergic neurons produce wakefulness. Methods Using vGlut2-cre mice, we transfected neurons in the PPT region with a viral vector coding for cre-dependent ChR2 tagged with fluorescent mCherry and implanted bilateral optical fibers above the PPT nuclei as well as EEG/EMG leads. Two weeks later, we administered blue laser light to activate ChR2-expressing neurons and recorded sleep/wake states. Results Activation of ChR2-expressing glutamatergic neurons during NREM sleep rapidly elicited wakefulness in a stimulation-frequency dependent manner, with higher frequencies producing wake more quickly and with longer duration. Random, automated stimulation for 10 s at 5 Hz over 24 h revealed that activation of glutamatergic PPT neurons produces rapid arousals form NREM sleep. Importantly, stimulation did not wake mice from REM sleep, suggesting that glutamatergic PPT signaling does not interfere with REM sleep. To map the target areas through which PPT glut neurons produce wakefulness, we used a viral tracer to visualize PPT glutamatergic projections, and then optogenetically stimulated terminals in 1) basal forebrain, 2) lateral hypothalamus, 3) thalamus, and 4) substantia nigra. We found that stimulating terminals in all of these regions woke mice from NREM sleep, and stimulating terminals in the basal forebrain and lateral hypothalamus produced a number of active wake behaviors such as locomotion. In contrast, stimulation of PPT glut soma and terminals in the thalamus and substantia nigra results mainly in quiet wakefulness. Conclusion Glutamatergic PPT neurons potently promote arousal from NREM sleep but not REM sleep, and the resulting wake behavior is modulated by different projection targets. Support NIH grant P01 - HL095491

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

10.1101/2021.05.14.444161 ◽

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.

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

Frontiers in Neuroscience ◽

10.3389/fnins.2021.709825 ◽

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.

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Time-of-day influence on exploratory behaviour of rats exposed to an unfamiliar environment

Behaviour ◽

10.1163/1568539x-00003224 ◽

2014 ◽

Vol 151 (14) ◽

pp. 1943-1966 ◽

Cited By ~ 3

Author(s):

Cássio M. Loss ◽

Sandro D. Córdova ◽

Sidia Maria Callegari-Jacques ◽

Diogo L. de Oliveira

Keyword(s):

Principal Component ◽

Time Of Day ◽

Temporal Organization ◽

Exploratory Behaviour ◽

Dark Phase ◽

Light Phase ◽

Home Base ◽

Plus Maze ◽

Male Wistar Rats ◽

Spatio Temporal

It is well known that rats exhibit elevated levels of activity during the dark phase and reduced levels during the light phase of the photoperiod cycle. However, the information about the influence of the time-of-day on the strategies used to explore the environment is still not understood. Here we tested the hypothesis that time-of-day influences the fine-scale exploratory behaviour of rats, measured in the open field (OF) test, and emotionality of rats, measured in the elevated plus maze (EPM) test. Adult male Wistar rats were subjected to the OF and EPM tests during Morning, Afternoon, or Evening sessions. In the OF, a principal component analysis (PCA) revealed that the Evening group exhibited longer duration of locomotion and rearing, and also higher distance travelled, trip length, inter-stop distance, number of stops and stops per trip compared to other groups. PCA also revealed that the Evening group exhibited shorter time spent at the home base, duration of locomotion along the perimeter and distance travelled along the perimeter compared to other groups. In the EPM test, there was no difference between the groups in any of the parameters evaluated. Our results indicate that the time-of-day may influence the spatio-temporal organization of exploration of rats subjected to unfamiliar environments. These alterations appear to be unrelated to differences in the emotional state of the animals.

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Gastrointestinal Vagal Afferents and Food Intake: Relevance of Circadian Rhythms

Nutrients ◽

10.3390/nu13030844 ◽

2021 ◽

Vol 13 (3) ◽

pp. 844

Author(s):

Amanda J. Page

Keyword(s):

Food Intake ◽

Shift Work ◽

Time Of Day ◽

Meal Size ◽

Vagal Afferents ◽

Diurnal Rhythms ◽

Dark Phase ◽

Light Phase ◽

Diet Induced Obesity ◽

The Impact

Gastrointestinal vagal afferents (VAs) play an important role in food intake regulation, providing the brain with information on the amount and nutrient composition of a meal. This is processed, eventually leading to meal termination. The response of gastric VAs, to food-related stimuli, is under circadian control and fluctuates depending on the time of day. These rhythms are highly correlated with meal size, with a nadir in VA sensitivity and increase in meal size during the dark phase and a peak in sensitivity and decrease in meal size during the light phase in mice. These rhythms are disrupted in diet-induced obesity and simulated shift work conditions and associated with disrupted food intake patterns. In diet-induced obesity the dampened responses during the light phase are not simply reversed by reverting back to a normal diet. However, time restricted feeding prevents loss of diurnal rhythms in VA signalling in high fat diet-fed mice and, therefore, provides a potential strategy to reset diurnal rhythms in VA signalling to a pre-obese phenotype. This review discusses the role of the circadian system in the regulation of gastrointestinal VA signals and the impact of factors, such as diet-induced obesity and shift work, on these rhythms.

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