Hugin+ neurons provide a link between sleep homeostat and circadian clock neurons

2021 ◽  
Vol 118 (47) ◽  
pp. e2111183118
Author(s):  
Jessica E. Schwarz ◽  
Anna N. King ◽  
Cynthia T. Hsu ◽  
Annika F. Barber ◽  
Amita Sehgal
Keyword(s):  
Locomotor Activity ◽  
Sleep Deprivation ◽  
Circadian Clock ◽  
Sleep Loss ◽  
Daily Cycle ◽  
Shaped Body ◽  
Recovery Sleep ◽  
Sleep Homeostat ◽  
Central Clock ◽  
Homeostatic Mechanisms

Sleep is controlled by homeostatic mechanisms, which drive sleep after wakefulness, and a circadian clock, which confers the 24-h rhythm of sleep. These processes interact with each other to control the timing of sleep in a daily cycle as well as following sleep deprivation. However, the mechanisms by which they interact are poorly understood. We show here that hugin+ neurons, previously identified as neurons that function downstream of the clock to regulate rhythms of locomotor activity, are also targets of the sleep homeostat. Sleep deprivation decreases activity of hugin+ neurons, likely to suppress circadian-driven activity during recovery sleep, and ablation of hugin+ neurons promotes sleep increases generated by activation of the homeostatic sleep locus, the dorsal fan-shaped body (dFB). Also, mutations in peptides produced by the hugin+ locus increase recovery sleep following deprivation. Transsynaptic mapping reveals that hugin+ neurons feed back onto central clock neurons, which also show decreased activity upon sleep loss, in a Hugin peptide–dependent fashion. We propose that hugin+ neurons integrate circadian and sleep signals to modulate circadian circuitry and regulate the timing of sleep.

scholarly journals A Circuit Mechanism Underlying Suppression of Circadian Signals by Homeostatic Sleep Drive

2020 ◽  
Author(s):  
Anna N. King ◽  
Jessica E. Schwarz ◽  
Cynthia T. Hsu ◽  
Annika F. Barber ◽  
Amita Sehgal
Keyword(s):  
Rest Period ◽  
Circadian System ◽  
Daily Cycle ◽  
Sleep Timing ◽  
Recovery Sleep ◽  
Circadian Control ◽  
Sleep Drive ◽  
Output Neurons ◽  
Central Clock ◽  
Homeostatic Mechanisms

AbstractSleep is controlled by homeostatic mechanisms, which drive sleep following periods of wakefulness, and a circadian clock, which regulates sleep timing in a daily cycle. Homeostatic sleep drive sometimes overrides the clock, such that recovery sleep after deprivation occurs outside the normal circadian rest period. However, mechanisms underlying this effect are unknown. We find that sleep-promoting dorsal fan-shaped body (dFB) neurons, effectors of homeostatic sleep in Drosophila, are presynaptic to hugin+ neurons, previously identified as circadian output neurons regulating locomotor activity rhythms. Sleep deprivation decreases hugin+ neuronal activity, which likely suppresses circadian control to promote recovery sleep driven by dFB neurons. Indeed, removal of hugin+ neurons increases sleep-promoting effects of dFB neurons. Trans-synaptic mapping reveals that hugin+ neurons feed back onto s-LNv central clock neurons, which also show Hugin-dependent decreased activity upon sleep loss. These findings identify a circuit-based mechanism through which sleep drive modulates the circadian system to promote recovery sleep following deprivation.

scholarly journals Circadian programming of the ellipsoid body sleep homeostat in Drosophila

2021 ◽  
Author(s):  
Tomas Andreani ◽  
Clark Rosensweig ◽  
Shiju Sisobhan ◽  
Emmanuel Ogunlana ◽  
Bill Kath ◽  
...  
Keyword(s):  
Gene Expression ◽  
Locomotor Activity ◽  
Sleep Deprivation ◽  
Circadian Clock ◽  
Molecular Mechanisms ◽  
Time Dependent ◽  
Ellipsoid Body ◽  
Sleep Homeostat ◽  
Presynaptic Protein ◽  
Activity Dependent

Homeostatic and circadian processes collaborate to appropriately time and consolidate sleep and wake. To understand how these processes are integrated, we scheduled brief sleep deprivation at different times of day in Drosophila and find elevated morning rebound compared to evening. These effects depend on discrete morning and evening clock neurons, independent of their roles in circadian locomotor activity. In the R5 ellipsoid body sleep homeostat, we identified elevated morning expression of activity dependent and presynaptic gene expression as well as the presynaptic protein BRUCHPILOT consistent with regulation by clock circuits. These neurons also display elevated calcium levels in response to sleep loss in the morning, but not the evening consistent with the observed time-dependent sleep rebound. These studies reveal the circuit and molecular mechanisms by which discrete circadian clock neurons program a homeostatic sleep center.

scholarly journals Residual, differential neurobehavioral deficits linger after multiple recovery nights following chronic sleep restriction or acute total sleep deprivation

SLEEP ◽  
2020 ◽  
Author(s):  
Erika M Yamazaki ◽  
Caroline A Antler ◽  
Charlotte R Lasek ◽  
Namni Goel
Keyword(s):  
Sleep Deprivation ◽  
Response Speed ◽  
Sleep Loss ◽  
Sleep Restriction ◽  
Total Sleep Deprivation ◽  
Psychomotor Vigilance Test ◽  
Recovery Sleep ◽  
Time In Bed ◽  
Neurobehavioral Deficits ◽  
Chronic Sleep

Abstract Study Objectives The amount of recovery sleep needed to fully restore well-established neurobehavioral deficits from sleep loss remains unknown, as does whether the recovery pattern differs across measures after total sleep deprivation (TSD) and chronic sleep restriction (SR). Methods In total, 83 adults received two baseline nights (10–12-hour time in bed [TIB]) followed by five 4-hour TIB SR nights or 36-hour TSD and four recovery nights (R1–R4; 12-hour TIB). Neurobehavioral tests were completed every 2 hours during wakefulness and a Maintenance of Wakefulness Test measured physiological sleepiness. Polysomnography was collected on B2, R1, and R4 nights. Results TSD and SR produced significant deficits in cognitive performance, increases in self-reported sleepiness and fatigue, decreases in vigor, and increases in physiological sleepiness. Neurobehavioral recovery from SR occurred after R1 and was maintained for all measures except Psychomotor Vigilance Test (PVT) lapses and response speed, which failed to completely recover. Neurobehavioral recovery from TSD occurred after R1 and was maintained for all cognitive and self-reported measures, except for vigor. After TSD and SR, R1 recovery sleep was longer and of higher efficiency and better quality than R4 recovery sleep. Conclusions PVT impairments from SR failed to reverse completely; by contrast, vigor did not recover after TSD; all other deficits were reversed after sleep loss. These results suggest that TSD and SR induce sustained, differential biological, physiological, and/or neural changes, which remarkably are not reversed with chronic, long-duration recovery sleep. Our findings have critical implications for the population at large and for military and health professionals.

137 Recovery Dynamics in a Biomathematical Model of Fatigue

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A56-A56
Author(s):  
Mark McCauley ◽  
Peter McCauley ◽  
Hans Van Dongen
Keyword(s):  
Sleep Deprivation ◽  
Goodness Of Fit ◽  
Sleep Loss ◽  
Sleep Restriction ◽  
Commercial Aviation ◽  
Circadian Misalignment ◽  
Total Sleep Deprivation ◽  
Homeostatic Process ◽  
Recovery Sleep

Abstract Introduction In commercial aviation and other operational settings where biomathematical models of fatigue are used for fatigue risk management, accurate prediction of recovery during rest periods following duty periods with sleep loss and/or circadian misalignment is critical. The recuperative potential of recovery sleep is influenced by a variety of factors, including long-term, allostatic effects of prior sleep/wake history. For example, recovery tends to be slower after sustained sleep restriction versus acute total sleep deprivation. Capturing such dynamics has proven to be challenging. Methods Here we focus on the dynamic biomathematical model of McCauley et al. (2013). In addition to a circadian process, this model features differential equations for sleep/wake regulation including a short-term sleep homeostatic process capturing change in the order of hours/days and a long-term allostatic process capturing change in the order of days/weeks. The allostatic process modulates the dynamics of the homeostatic process by shifting its equilibrium setpoint, which addresses recently observed phenomena such as reduced vulnerability to sleep loss after banking sleep. It also differentiates the build-up and recovery rates of fatigue under conditions of chronic sleep restriction versus acute total sleep deprivation; nonetheless, it does not accurately predict the disproportionately rapid recovery seen after total sleep deprivation. To improve the model, we hypothesized that the homeostatic process may also modulate the allostatic process, with the magnitude of this effect scaling as a function of time awake. Results To test our hypothesis, we added a parameter to the model to capture modulation by the homeostatic process of the allostatic process build-up during wakefulness and dissipation during sleep. Parameter estimation using previously published laboratory datasets of fatigue showed this parameter as significantly different from zero (p<0.05) and yielding a 10%–20% improvement in goodness-of-fit for recovery without adversely affecting goodness-of-fit for pre-recovery days. Conclusion Inclusion of a modulation effect of the allostatic process by the homeostatic process improved prediction accuracy in a variety of sleep loss and circadian misalignment scenarios. In addition to operational relevance for duty/rest scheduling, this finding has implications for understanding mechanisms underlying the homeostatic and allostatic processes of sleep/wake regulation. Support (if any) Federal Express Corporation

Sleep Deprivation Induces Neuroinflammation and Depressive-like Behaviors by Impairing the Regulation of Circadian Clock Genes Expression in Rats

2020 ◽  
Author(s):  
Chen Xing ◽  
Yanzhao Zhou ◽  
Huan Xu ◽  
Mengnan Ding ◽  
Yifan Zhang ◽  
...  
Keyword(s):  
Sleep Deprivation ◽  
Circadian Clock ◽  
Glial Cell ◽  
Hpa Axis ◽  
Calcium Binding ◽  
Cell Activation ◽  
Clock Genes ◽  
Sleep Loss ◽  
Genes Expression ◽  
Circadian Clock Genes

Abstract Background: Sleep loss leads to a spectrum of mood disorders such as anxiety, cognitive dysfunction and motor coordination impairment in many individuals. However, the underlying mechanisms are largely unknown. Methods: In this study, we examined the effects of sleep deprivation (SD) on depression and the mechanism by subjecting rats to a slowly rotating platform for 3 days to mimic the process of sleep loss. Sleep-deprived animals were tested behaviorally for anxiety- and depressive-like behaviors. We further studied the effects of SD on hypothalamic-pituitary-adrenal (HPA) axis activity, and at the end of the experiment, brains were collected to measure the circadian clock genes expression in the hypothalamus, glial cell activation and inflammatory cytokine alterations. Results: Our results indicated that SD for 3 days resulted in anxiety- and depressive-like behaviors. SD exaggerated cortisol response to HPA axis, significantly altered the mRNA profile of circadian clock genes, and induced neuroinflammation by increasing the expression of glial cell markers, including the microglial marker ionized calcium-binding adapter molecule 1 (Iba1) and the astroglial marker glial fibrillary acidic protein (GFAP). The expression of M1 and M2 microglial markers (Arg-1 and CD206, respectively) and pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) were increased in the brain. Conclusion: These results indicated that SD for 3 days induced anxiety- and depression-like behaviors in rats by impairing the regulation of circadian clock genes and inducing neuroinflammation, ultimately resulting in brain injury.

scholarly journals Effects of Sleep Deprivation on Brain Bioenergetics, Sleep, and Cognitive Performance in Cocaine-Dependent Individuals

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
George H. Trksak ◽  
Bethany K. Bracken ◽  
J. Eric Jensen ◽  
David T. Plante ◽  
David M. Penetar ◽  
...  
Keyword(s):  
Sleep Deprivation ◽  
Cognitive Performance ◽  
Sleep Loss ◽  
Continuous Performance ◽  
Digit Symbol ◽  
Continuous Performance Task ◽  
Performance Task ◽  
Recovery Sleep ◽  
Symbol Substitution ◽  
Healthy Control

In cocaine-dependent individuals, sleep is disturbed during cocaine use and abstinence, highlighting the importance of examining the behavioral and homeostatic response to acute sleep loss in these individuals. The current study was designed to identify a differential effect of sleep deprivation on brain bioenergetics, cognitive performance, and sleep between cocaine-dependent and healthy control participants. 14 healthy control and 8 cocaine-dependent participants experienced consecutive nights of baseline, total sleep deprivation, and recovery sleep in the research laboratory. Participants underwent[31]P magnetic resonance spectroscopy (MRS) brain imaging, polysomnography, Continuous Performance Task, and Digit Symbol Substitution Task. Following recovery sleep,[31]P MRS scans revealed that cocaine-dependent participants exhibited elevated global brainβ-NTP (direct measure of adenosine triphosphate),α-NTP, and total NTP levels compared to those of healthy controls. Cocaine-dependent participants performed worse on the Continuous Performance Task and Digit Symbol Substitution Task at baseline compared to healthy control participants, but sleep deprivation did not worsen cognitive performance in either group. Enhancements of brain ATP levels in cocaine dependent participants following recovery sleep may reflect a greater impact of sleep deprivation on sleep homeostasis, which may highlight the importance of monitoring sleep during abstinence and the potential influence of sleep loss in drug relapse.

scholarly journals Genetic Markers of Differential Vulnerability to Sleep Loss in Adults

Genes ◽  
2021 ◽  
Vol 12 (9) ◽  
pp. 1317
Author(s):  
Courtney E. Casale ◽  
Namni Goel
Keyword(s):  
Sleep Deprivation ◽  
Genetic Markers ◽  
Clock Genes ◽  
Association Studies ◽  
Sleep Loss ◽  
Future Research ◽  
Candidate Gene Approach ◽  
Genome Wide Association Studies ◽  
Recovery Sleep ◽  
Differential Vulnerability

In this review, we discuss reports of genotype-dependent interindividual differences in phenotypic neurobehavioral responses to total sleep deprivation or sleep restriction. We highlight the importance of using the candidate gene approach to further elucidate differential resilience and vulnerability to sleep deprivation in humans, although we acknowledge that other omics techniques and genome-wide association studies can also offer insights into biomarkers of such vulnerability. Specifically, we discuss polymorphisms in adenosinergic genes (ADA and ADORA2A), core circadian clock genes (BHLHE41/DEC2 and PER3), genes related to cognitive development and functioning (BDNF and COMT), dopaminergic genes (DRD2 and DAT), and immune and clearance genes (AQP4, DQB1*0602, and TNFα) as potential genetic indicators of differential vulnerability to deficits induced by sleep loss. Additionally, we review the efficacy of several countermeasures for the neurobehavioral impairments induced by sleep loss, including banking sleep, recovery sleep, caffeine, and naps. The discovery of reliable, novel genetic markers of differential vulnerability to sleep loss has critical implications for future research involving predictors, countermeasures, and treatments in the field of sleep and circadian science.

scholarly journals Unique transcriptional signatures of sleep loss across independently evolved cavefish populations

2019 ◽  
Author(s):  
Suzanne E. McGaugh ◽  
Courtney N. Passow ◽  
James Brian Jaggard ◽  
Bethany A. Stahl ◽  
Alex C. Keene
Keyword(s):  
Sleep Deprivation ◽  
Sleep Duration ◽  
Differentially Expressed Genes ◽  
Sleep Loss ◽  
Differentially Expressed ◽  
Molecular Response ◽  
Recovery Sleep ◽  
Sleep Homeostasis ◽  
Surface Population ◽  
Physiological Homeostasis

AbstractAnimals respond to sleep loss with compensatory rebound sleep, and this is thought to be critical for the maintenance of physiological homeostasis. Sleep duration varies dramatically across animal species, but it is not known whether evolutionary differences in sleep duration are associated with differences in sleep homeostasis. The Mexican cavefish, Astyanax mexicanus, has emerged as a powerful model for studying the evolution of sleep. While eyed surface populations of A. mexicanus sleep approximately eight hours each day, multiple blind cavefish populations have converged on sleep patterns that total as little as two hours each day, providing the opportunity to examine whether the evolution of sleep loss is accompanied by changes in sleep homeostasis. Here, we examine the behavioral and molecular response to sleep deprivation across four independent populations of A. mexicanus. Our behavioral analysis indicates that surface fish and all three cavefish populations display robust recovery sleep during the day following nighttime sleep deprivation, suggesting sleep homeostasis remains intact in cavefish. We profiled transcriptome-wide changes associated with sleep deprivation in surface fish and cavefish. While the total number of differentially expressed genes was not greater for the surface population, the surface population exhibited the highest number of uniquely differentially expressed genes than any other population. Strikingly, a majority of the differentially expressed genes are unique to individual cave populations, suggesting unique expression responses are exhibited across independently evolved cavefish populations. Together, these findings suggest sleep homeostasis is intact in cavefish despite a dramatic reduction in overall sleep duration.

Self-Reported Sleep Need, Subjective Resilience, and Cognitive Performance Following Sleep Loss and Recovery Sleep

2020 ◽  
pp. 003329411989989
Author(s):  
Janna Mantua ◽  
Allison J. Brager ◽  
Sara E. Alger ◽  
Folarin Adewle ◽  
Lillian Skeiky ◽  
...  
Keyword(s):  
Sleep Deprivation ◽  
Cognitive Performance ◽  
Test Performance ◽  
Cost Effective ◽  
Sleep Loss ◽  
Subjective Sleep ◽  
Psychomotor Vigilance Test ◽  
Recovery Sleep ◽  
Vigilance Test ◽  
Psychomotor Vigilance

Objective Individuals vary in response to sleep loss: some individuals are “vulnerable” and demonstrate cognitive decrements following insufficient sleep, while others are “resistant” and maintain baseline cognitive capability. Physiological markers (e.g., genetic polymorphisms) have been identified that can predict relative vulnerability. However, a quick, cost-effective, and feasible subjective predictor tool has not been developed. The objective of the present study was to determine whether two factors—“subjective sleep need” and “subjective resilience”—predict cognitive performance following sleep deprivation. Methods Twenty-seven healthy, sleep-satiated young adults participated. These individuals were screened for sleep disorders, comorbidities, and erratic sleep schedules. Prior to 40 hours of in-laboratory total sleep deprivation, participants were questioned on their subjective sleep need and completed a validated resilience scale. During and after sleep deprivation, participants completed a 5-minute psychomotor vigilance test every 2 hours. Results Both subjective resilience and subjective sleep need individually failed to predict performance during sleep loss. However, these two measures interacted to predict performance. Individuals with low resilience and low sleep need had poorer cognitive performance during sleep loss. However, in individuals with medium or high resilience, psychomotor vigilance test performance was not predicted by subjective sleep need. Higher resilience may be protective against sleep loss-related neurobehavioral impairments in the context of subjective sleep need. Conclusions Following sleep loss (and recovery sleep), trait resilient individuals may outperform those with lower resiliency on real-world tasks that require continuous attention. Future studies should determine whether the present findings generalize to other, operationally relevant tasks and additional cognitive domains.

scholarly journals Recovery sleep after extended wakefulness restores elevated A1adenosine receptor availability in the human brain

2017 ◽  
Vol 114 (16) ◽  
pp. 4243-4248 ◽  
Author(s):  
David Elmenhorst ◽  
Eva-Maria Elmenhorst ◽  
Eva Hennecke ◽  
Tina Kroll ◽  
Andreas Matusch ◽  
...  
Keyword(s):  
Sleep Deprivation ◽  
Human Brain ◽  
Cognitive Performance ◽  
Brain Regions ◽  
Sleep Loss ◽  
Control Group ◽  
Sleep Episode ◽  
Recovery Sleep ◽  
Positron Emission ◽  
Performance Impairment

Adenosine and functional A1adenosine receptor (A1AR) availability are supposed to mediate sleep–wake regulation and cognitive performance. We hypothesized that cerebral A1AR availability after an extended wake period decreases to a well-rested state after recovery sleep. [18F]CPFPX positron emission tomography was used to quantify A1AR availability in 15 healthy male adults after 52 h of sleep deprivation and following 14 h of recovery sleep. Data were additionally compared with A1AR values after 8 h of baseline sleep from an earlier dataset. Polysomnography, cognitive performance, and sleepiness were monitored. Recovery from sleep deprivation was associated with a decrease in A1AR availability in several brain regions, ranging from 11% (insula) to 14% (striatum). A1AR availabilities after recovery did not differ from baseline sleep in the control group. The degree of performance impairment, sleepiness, and homeostatic sleep-pressure response to sleep deprivation correlated negatively with the decrease in A1AR availability. Sleep deprivation resulted in a higher A1AR availability in the human brain. The increase that was observed after 52 h of wakefulness was restored to control levels during a 14-h recovery sleep episode. Individuals with a large increase in A1AR availability were more resilient to sleep-loss effects than those with a subtle increase. This pattern implies that differences in endogenous adenosine and A1AR availability might be causal for individual responses to sleep loss.

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