scholarly journals Genetic lesioning of histamine neurons increases sleep–wake fragmentation and reveals their contribution to modafinil-induced wakefulness

SLEEP ◽  
2019 ◽  
Vol 42 (5) ◽  
Author(s):  
Xiao Yu ◽  
Ying Ma ◽  
Edward C Harding ◽  
Raquel Yustos ◽  
Alexei L Vyssotski ◽  
...  
Keyword(s):  
Sleep Deprivation ◽  
Eye Movement ◽  
Knockout Mice ◽  
Histidine Decarboxylase ◽  
Nrem Sleep ◽  
Delta Power ◽  
Adult Mice ◽  
Sleep Homeostasis ◽  
Normal Sleep ◽  
Wake State

Abstract Acute chemogenetic inhibition of histamine (HA) neurons in adult mice induced nonrapid eye movement (NREM) sleep with an increased delta power. By contrast, selective genetic lesioning of HA neurons with caspase in adult mice exhibited a normal sleep–wake cycle overall, except at the diurnal start of the lights-off period, when they remained sleepier. The amount of time spent in NREM sleep and in the wake state in mice with lesioned HA neurons was unchanged over 24 hr, but the sleep–wake cycle was more fragmented. Both the delayed increase in wakefulness at the start of the night and the sleep–wake fragmentation are similar phenotypes to histidine decarboxylase knockout mice, which cannot synthesize HA. Chronic loss of HA neurons did not affect sleep homeostasis after sleep deprivation. However, the chronic loss of HA neurons or chemogenetic inhibition of HA neurons did notably reduce the ability of the wake-promoting compound modafinil to sustain wakefulness. Thus, part of modafinil’s wake-promoting actions arise through the HA system.

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 Galanin neurons in the hypothalamus link sleep homeostasis, body temperature and actions of the α2 adrenergic agonist dexmedetomidine

2019 ◽  
Author(s):  
Ying Ma ◽  
Giulia Miracca ◽  
Xiao Yu ◽  
Edward C. Harding ◽  
Andawei Miao ◽  
...  
Keyword(s):  
Body Temperature ◽  
Sleep Deprivation ◽  
Core Body Temperature ◽  
Neuronal Cell ◽  
Nrem Sleep ◽  
Temperature Characteristic ◽  
Adrenergic Agonist ◽  
Delta Power ◽  
Recovery Sleep ◽  
Sleep Homeostasis

AbstractSleep deprivation induces a characteristic rebound in NREM sleep accompanied by an immediate increase in the power of delta (0.5 - 4 Hz) oscillations, proportional to the prior time awake. To test the idea that galanin neurons in the mouse lateral preoptic hypothalamus (LPO) regulate this sleep homeostasis, they were selectively genetically ablated. The baseline sleep architecture of LPO-ΔGal mice became heavily fragmented, their average core body temperature permanently increased (by about 2°C) and the diurnal variations in body temperature across the sleep-wake cycle also markedly increased. Additionally, LPO-ΔGal mice showed a striking spike in body temperature and increase in wakefulness at a time (ZT24) when control mice were experiencing the opposite - a decrease in body temperature and becoming maximally sleepy (start of “lights on”). After sleep deprivation sleep homeostasis was largely abolished in LPO-ΔGal mice: the characteristic increase in the delta power of NREM sleep following sleep deprivation was absent, suggesting that LPO galanin neurons track the time spent awake. Moreover, the amount of recovery sleep was substantially reduced over the following hours. We also found that the α2 adrenergic agonist dexmedetomidine, used for long-term sedation during intensive care, requires LPO galanin neurons to induce both the NREM-like state with increased delta power and the reduction in body temperature, characteristic features of this drug. This suggests that dexmedetomidine over-activates the natural sleep homeostasis pathway via galanin neurons. Collectively, the results emphasize that NREM sleep and the concurrent reduction in body temperature are entwined at the circuit level.SignificanceCatching up on lost sleep (sleep homeostasis) is a common phenomenon in mammals, but there is no circuit explanation for how this occurs. We have discovered that galanin neurons in the hypothalamus are essential for sleep homeostasis as well as for the control of body temperature. This is the first time that a neuronal cell type has been identified that underlies sleep homeostasis. Moreover, we show that activation of these galanin neurons are also essential for the actions of the α2 adrenergic agonist dexmedetomidine, which induces both hypothermia together with powerful delta oscillations resembling NREM sleep. Thus, sleep homeostasis, temperature control and sedation by α2 adrenergic agonists can all be linked at the circuit level by hypothalamic galanin neurons.

Sleep after arousal from hibernation is not homeostatically regulated

1999 ◽  
Vol 276 (2) ◽  
pp. R522-R529 ◽  
Author(s):  
Jennie E. Larkin ◽  
H. Craig Heller
Keyword(s):  
Sleep Deprivation ◽  
Brain Function ◽  
Extended Period ◽  
Nrem Sleep ◽  
Wave Activity ◽  
Ground Squirrels ◽  
Recovery Sleep ◽  
Sleep Homeostasis ◽  
Homeostatic Response ◽  
Periodic Arousals

Electroencephalographic slow-wave activity (SWA) in non-rapid eye movement (NREM) sleep is directly related to prior sleep/wake history, with high levels of SWA following extended periods of wake. Therefore, SWA has been thought to reflect the level of accumulated sleep need. The discovery that euthermic intervals between hibernation bouts are spent primarily in sleep and that this sleep is characterized by high and monotonically declining SWA has led to speculation that sleep homeostasis may play a fundamental role in the regulation of the timing of bouts of hibernation and periodic arousals to euthermia. It was proposed that because the SWA profile seen after arousal from hibernation is strikingly similar to what is seen in nonhibernating mammals after extended periods of wakefulness, that hibernating mammals may arouse from hibernation with significant accumulated sleep need. This sleep need may accumulate during hibernation because the low brain temperatures during hibernation may not be compatible with sleep restorative processes. In the present study, golden-mantled ground squirrels were sleep deprived during the first 4 h of interbout euthermia by injection of caffeine (20 mg/kg ip). We predicted that if the SWA peaks after bouts of hibernation reflected a homeostatic response to an accumulated sleep need, sleep deprivation should simply have displaced and possibly augmented the SWA to subsequent recovery sleep. Instead we found that after caffeine-induced sleep deprivation of animals just aroused from hibernation, the anticipated high SWA typical of recovery sleep did not occur. Similar results were found in a study that induced sleep deprivation by gentle handling (19). These findings indicate that the SWA peak immediately after hibernation does not represent homeostatic regulation of NREM sleep, as it normally does after prolonged wakefulness during euthermia, but instead may reflect some other neurological process in the recovery of brain function from an extended period at low temperature.

scholarly journals Pharmacological Modulation of Sleep Homeostasis in Rat: Novel Effects of an mGluR2/3 Antagonist

SLEEP ◽  
2019 ◽  
Vol 42 (9) ◽  
Author(s):  
Nicola Hanley ◽  
Jerome Paulissen ◽  
Brian J Eastwood ◽  
Gary Gilmour ◽  
Sally Loomis ◽  
...  
Keyword(s):  
Eye Movement ◽  
Functional Capacity ◽  
Rem Sleep ◽  
Critical Role ◽  
Nrem Sleep ◽  
Rapid Eye Movement ◽  
Negative Consequences ◽  
Promoting Effect ◽  
Two Phase ◽  
Sleep Homeostasis

Abstract Increasing vigilance without incurring the negative consequences of extended wakefulness such as daytime sleepiness and cognitive impairment is a major challenge in treating many sleep disorders. The present work compares two closely related mGluR2/3 antagonists LY3020371 and LY341495 with two well-known wake-promoting compounds caffeine and d-amphetamine. Sleep homeostasis properties were explored in male Wistar rats by manipulating levels of wakefulness via (1) physiological sleep restriction (SR), (2) pharmacological action, or (3) a combination of these. A two-phase nonlinear mixed-effects model combining a quadratic and exponential function at an empirically estimated join point allowed the quantification of wake-promoting properties and any subsequent sleep rebound. A simple response latency task (SRLT) following SR assessed functional capacity of sleep-restricted animals treated with our test compounds. Caffeine and d-amphetamine increased wakefulness with a subsequent full recovery of non-rapid eye movement (NREM) and rapid eye movement (REM) sleep and were unable to fully reverse SR-induced impairments in SRLT. In contrast, LY3020371 increased wakefulness with no subsequent elevation of NREM sleep, delta power, delta energy, or sleep bout length and count, yet REM sleep recovered above baseline levels. Prior sleep pressure obtained using an SR protocol had no impact on the wake-promoting effect of LY3020371 and NREM sleep rebound remained blocked. Furthermore, LY341495 increased functional capacity across SRLT measures following SR. These results establish the critical role of glutamate in sleep homeostasis and support the existence of independent mechanisms for NREM and REM sleep homeostasis.

NREM delta stimulation following MK-801 is a response of sleep systems

1996 ◽  
Vol 76 (6) ◽  
pp. 3714-3720 ◽  
Author(s):  
I. G. Campbell ◽  
I. Feinberg
Keyword(s):  
Sleep Deprivation ◽  
Eye Movement ◽  
Time Course ◽  
Sleep Onset ◽  
Nrem Sleep ◽  
Rapid Eye Movement ◽  
Mk 801 ◽  
Regulatory Systems ◽  
Sleep Centers ◽  
Electroencephalogram Eeg

1. We have previously shown that noncompetitive blockade of the N-methyl-D-aspartate (NMDA)-gated cation channel with ketamine or Dizocilpine maleate (MK-801) increases the intensity of non-rapid-eye-movement (NREM) delta during subsequent sleep. This delta increase [measured as integrated amplitude (IA) in 1- to 4-Hz electroencephalogram (EEG)] occurs in the 12-h period following intraperitoneal injection. However, the 12 h after drug injection is also the period in which these drugs induce neurotoxic changes, raising the possibility that the increased delta represents toxic EEG slowing rather than an increase in the physiological delta waves of NREM sleep. 2. We hypothesized that the time course of delta stimulation could be separated from the time course of neurotoxicity. We tested this hypothesis by injecting 0.3 mg/kg MK-801 at the start of the dark period (DP) and depriving rats of sleep until the onset of the light period (LP) 12 h later. 3. There were two control groups: one received MK-801 at the start of the DP with no further manipulation, and the second received a saline injection at DP onset followed by 12 h of sleep deprivation. The dependent variable was the amount of delta IA in the LP, whose onset was 12 h after MK-801 injection. Total IA in the LP was significantly greater in rats that received MK-801 followed by sleep deprivation than in rats that received sleep deprivation alone or MK-801 alone. 4. This finding indicates that delta stimulation by MK-801 is maintained over 12 h of waking, indicating that the delta increase is not due to toxic EEG slowing or persisting MK-801. Instead, NMDA channel blockade by MK-801 increases the homeostatic need for delta or else directly alters sleep regulatory systems. We speculate that these effects are mediated by hypothalamic sleep centers through control of neuroendocrine pulses that produce both NREM and rapid-eye-movement sleep. 5. Imposing a period of waking between drug administration and sleep onset may prove a generally useful strategy for determining whether a drug affects the homeostatic need for sleep or acutely stimulates sleep systems. This strategy can also help distinguish between toxic and physiological increases in delta EEG.

scholarly journals Global field synchronization reveals rapid eye movement sleep as most synchronized brain state in the human EEG

2016 ◽  
Vol 3 (10) ◽  
pp. 160201 ◽  
Author(s):  
Peter Achermann ◽  
Thomas Rusterholz ◽  
Roland Dürr ◽  
Thomas König ◽  
Leila Tarokh
Keyword(s):  
Functional Connectivity ◽  
Sleep Deprivation ◽  
Eye Movement ◽  
Rem Sleep ◽  
Nrem Sleep ◽  
Brain Regions ◽  
Global Field ◽  
Brain State ◽  
Rapid Eye Movement ◽  
Eyes Closed

Sleep is characterized by a loss of consciousness, which has been attributed to a breakdown of functional connectivity between brain regions. Global field synchronization (GFS) can estimate functional connectivity of brain processes. GFS is a frequency-dependent measure of global synchronicity of multi-channel EEG data. Our aim was to explore and extend the hypothesis of disconnection during sleep by comparing GFS spectra of different vigilance states. The analysis was performed on eight healthy adult male subjects. EEG was recorded during a baseline night, a recovery night after 40 h of sustained wakefulness and at 3 h intervals during the 40 h of wakefulness. Compared to non-rapid eye movement (NREM) sleep, REM sleep showed larger GFS values in all frequencies except in the spindle and theta bands, where NREM sleep showed a peak in GFS. Sleep deprivation did not affect GFS spectra in REM and NREM sleep. Waking GFS values were lower compared with REM and NREM sleep except for the alpha band. Waking alpha GFS decreased following sleep deprivation in the eyes closed condition only. Our surprising finding of higher synchrony during REM sleep challenges the view of REM sleep as a desynchronized brain state and may provide insight into the function of REM sleep.

Normal Sleep in Childhood

2021 ◽  
pp. 33-48
Author(s):  
Hovig K. Artinian ◽  
Mary Anne Tablizo ◽  
Manisha Witmans
Keyword(s):  
Eye Movement ◽  
Nrem Sleep ◽  
Rapid Eye Movement ◽  
Respiratory Parameters ◽  
Normal Sleep ◽  
Brain Changes ◽  
And Behavior ◽  
Changes Over Time ◽  
The Brain ◽  
Critical Process

Sleep is a critical process in children in that it influences all aspects of physiological functioning, development, and behavior. The two types of sleep, rapid eye movement (REM) sleep and non–rapid eye movement (NREM) sleep, are inherent throughout life; however, the sleep architecture and sleep duration changes over time as the brain changes from the newborn period to adulthood. There are hallmarks related to sleep architectural changes that are specific and unique to the different age ranges. Although the process and neuromodulation of sleep is similar across the life span, there are attributes that are different in children compared to adults. There are also physiological differences in the brain waves and changes in respiratory parameters. This chapter highlights normal sleep in children.

scholarly journals Lempel-Ziv complexity of cortical activity during sleep and waking in rats

2015 ◽  
Vol 113 (7) ◽  
pp. 2742-2752 ◽  
Author(s):  
Daniel Abásolo ◽  
Samantha Simons ◽  
Rita Morgado da Silva ◽  
Giulio Tononi ◽  
Vladyslav V. Vyazovskiy
Keyword(s):  
Sleep Deprivation ◽  
Eye Movement ◽  
Brain Activity ◽  
Temporal Structure ◽  
Nrem Sleep ◽  
Brain State ◽  
Rapid Eye Movement ◽  
Sleep Regulation ◽  
Spatio Temporal ◽  
Underlying Mechanisms

Understanding the dynamics of brain activity manifested in the EEG, local field potentials (LFP), and neuronal spiking is essential for explaining their underlying mechanisms and physiological significance. Much has been learned about sleep regulation using conventional EEG power spectrum, coherence, and period-amplitude analyses, which focus primarily on frequency and amplitude characteristics of the signals and on their spatio-temporal synchronicity. However, little is known about the effects of ongoing brain state or preceding sleep-wake history on the nonlinear dynamics of brain activity. Recent advances in developing novel mathematical approaches for investigating temporal structure of brain activity based on such measures, as Lempel-Ziv complexity (LZC) can provide insights that go beyond those obtained with conventional techniques of signal analysis. Here, we used extensive data sets obtained in spontaneously awake and sleeping adult male laboratory rats, as well as during and after sleep deprivation, to perform a detailed analysis of cortical LFP and neuronal activity with LZC approach. We found that activated brain states—waking and rapid eye movement (REM) sleep are characterized by higher LZC compared with non-rapid eye movement (NREM) sleep. Notably, LZC values derived from the LFP were especially low during early NREM sleep after sleep deprivation and toward the middle of individual NREM sleep episodes. We conclude that LZC is an important and yet largely unexplored measure with a high potential for investigating neurophysiological mechanisms of brain activity in health and disease.

scholarly journals Multicomponent Analysis of Sleep Using Electrocortical, Respiratory, Autonomic and Hemodynamic Signals Reveals Distinct Features of Stable and Unstable NREM and REM Sleep

2020 ◽  
Vol 11 ◽  
Author(s):  
Christopher Wood ◽  
Matt Travis Bianchi ◽  
Chang-Ho Yun ◽  
Chol Shin ◽  
Robert Joseph Thomas
Keyword(s):  
Blood Pressure ◽  
Sleep Apnea ◽  
Eye Movement ◽  
Rem Sleep ◽  
Nrem Sleep ◽  
Slow Oscillation ◽  
Rapid Eye Movement ◽  
Sinus Arrhythmia ◽  
Delta Power ◽  
High Loop

A new concept of non-rapid eye movement (NREM) and rapid eye movement (REM) sleep is proposed, that of multi-component integrative states that define stable and unstable sleep, respectively, NREMS, NREMUS REMS, and REMUS. Three complementary data sets are used: obstructive sleep apnea (20), healthy subjects (11), and high loop gain sleep apnea (50). We use polysomnography (PSG) with beat-to-beat blood pressure monitoring, and electrocardiogram (ECG)-derived cardiopulmonary coupling (CPC) analysis to demonstrate a bimodal, rather than graded, characteristic of NREM sleep. Stable NREM (NREMS) is characterized by high probability of occurrence of the <1 Hz slow oscillation, high delta power, stable breathing, blood pressure dipping, strong sinus arrhythmia and vagal dominance, and high frequency CPC. Conversely, unstable NREM (NREMUS) has the opposite features: a fragmented and discontinuous <1 Hz slow oscillation, non-dipping of blood pressure, unstable respiration, cyclic variation in heart rate, and low frequency CPC. The dimension of NREM stability raises the possibility of a comprehensive integrated multicomponent network model of NREM sleep which captures sleep onset (e.g., ventrolateral preoptic area-based sleep switch) processes, synaptic homeostatic delta power kinetics, and the interaction of global and local sleep processes as reflected in the spatiotemporal evolution of cortical “UP” and “DOWN” states, while incorporating the complex dynamics of autonomic-respiratory-hemodynamic systems during sleep. Bimodality of REM sleep is harder to discern in health. However, individuals with combined obstructive and central sleep apnea allows ready recognition of REMS and REMUS (stable and unstable REM sleep, respectively), especially when there is a discordance of respiratory patterns in relation to conventional stage of sleep.

332 Non-REM EEG Spectral Power at Baseline and After Total Sleep Deprivation in Individuals with Sleep-Onset Insomnia

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A133-A133
Author(s):  
Myles Finlay ◽  
Devon Hansen ◽  
Lillian Skeiky ◽  
Hans Van Dongen
Keyword(s):  
Sleep Deprivation ◽  
Rem Sleep ◽  
Spectral Power ◽  
Sleep Onset ◽  
Sleep Eeg ◽  
Alpha Power ◽  
Healthy Controls ◽  
Total Sleep Deprivation ◽  
Delta Power ◽  
Sleep Homeostasis

Abstract Introduction The baseline non-REM sleep EEG of individuals with insomnia has been found to display increased spectral power at frequencies >14Hz, which may reflect hyperarousal. There is some evidence in this population of reduced slow wave activity after total sleep deprivation (TSD), potentially indicating altered sleep homeostasis. We investigated non-REM sleep EEG spectra at baseline and after TSD in individuals with sleep-onset insomnia. Methods 10 individuals with sleep-onset insomnia and 5 healthy controls (ages 22-40y, 11 females) completed a 5-day laboratory study with an adaptation night, baseline night, assignment to 38h TSD (n=5 insomnia, n=5 control) or equivalent non-TSD control (n=5 insomnia), and recovery night. Sleep periods were 10h (22:00-08:00) with digital polysomnography (250Hz; Nihon Kohden). Following artifact rejection, 5s subepochs of the non-REM (stages N2, N3) sleep EEG (C3-M2 derivation) in baseline and recovery nights were subjected to spectral analysis. Spectra (0.2Hz bins) were averaged over subepochs in 30s epochs. Repeated-measures ANOVA compared baseline spectra between insomnia and controls, and baseline-recovery difference spectra between TSD insomnia, non-TSD insomnia, and TSD controls. Results Average non-REM sleep amount was 5.9 at baseline, increasing by 1.1h after TSD, with no differences between groups (p≥0.20). At baseline, the insomnia group showed increased power in theta/alpha (~4–12Hz), reaching significance in the lower spindle range, compared to controls (p<0.05). As anticipated, no differences emerged between baseline and recovery nights in the non-TSD insomnia group. However, the TSD insomnia group showed increased delta (~1–3Hz) and theta/alpha (~6–10Hz) power (p<0.05) during recovery. Healthy controls showed expected power increases in delta and lower spindle range, and decreases in upper spindle range (~14–15Hz), after TSD (p<0.05). Conclusion Compared to healthy controls, individuals with sleep-onset insomnia showed increased non-REM sleep EEG power in the theta/alpha bands and low spindle frequency range, with further significant increases in theta/alpha in addition to delta power following TSD, despite small sample size. The increase in delta power following TSD was equivalent to that in healthy controls, suggesting no sleep homeostasis abnormality. Whether the elevated theta/alpha power may be related to hyperarousal is unclear. Support (if any) ONR grant N00014-13-C-0063

Sign in / Sign up

Export Citation Format

Share Document