scholarly journals Hypocretin (orexin) is critical in sustaining theta/gamma-rich waking behaviors that drive sleep need

2017 ◽  
Vol 114 (27) ◽  
pp. E5464-E5473 ◽  
Author(s):  
Anne Vassalli ◽  
Paul Franken

Hcrt gene inactivation in mice leads to behavioral state instability, abnormal transitions to paradoxical sleep, and cataplexy, hallmarks of narcolepsy. Sleep homeostasis is, however, considered unimpaired in patients and narcoleptic mice. We find that whereas Hcrtko/ko mice respond to 6-h sleep deprivation (SD) with a slow-wave sleep (SWS) EEG δ (1.0 to 4.0 Hz) power rebound like WT littermates, spontaneous waking fails to induce a δ power reflecting prior waking duration. This correlates with impaired θ (6.0 to 9.5 Hz) and fast-γ (55 to 80 Hz) activity in prior waking. We algorithmically identify a theta-dominated wakefulness (TDW) substate underlying motivated behaviors and typically preceding cataplexy in Hcrtko/ko mice. Hcrtko/ko mice fully implement TDW when waking is enforced, but spontaneous TDW episode duration is greatly reduced. A reformulation of the classic sleep homeostasis model, where homeostatic pressure rises exclusively in TDW rather than all waking, predicts δ power dynamics both in Hcrtko/ko and WT mouse baseline and recovery SWS. The low homeostatic impact of Hcrtko/ko mouse spontaneous waking correlates with decreased cortical expression of neuronal activity-related genes (notably Bdnf, Egr1/Zif268, and Per2). Thus, spontaneous TDW stability relies on Hcrt to sustain θ/fast-γ network activity and associated plasticity, whereas other arousal circuits sustain TDW during SD. We propose that TDW identifies a discrete global brain activity mode that is regulated by context-dependent neuromodulators and acts as a major driver of sleep homeostasis. Hcrt loss in Hcrtko/ko mice causes impaired TDW maintenance in baseline wake and blunted δ power in SWS, reproducing, respectively, narcolepsy excessive daytime sleepiness and poor sleep quality.

2017 ◽  
Author(s):  
Sha Li ◽  
Paul Franken ◽  
Anne Vassalli

AbstractNoradrenaline (NA) and hypocretins/orexins (HCRT), and their receptors, dynamically modulate the circuits that configure behavioral states, and their associated oscillatory activities. Salient stimuli activate spiking of locus coeruleus noradrenergic (NALC) cells, inducing NA release and brain-wide noradrenergic signalling, thus resetting network activity, and mediating an orienting response. Hypothalamic HCRT neurons provide one of the densest input to NALC cells. To functionally address the HCRT-to-NA connection, we selectively disrupted the Hcrtr1 gene in NA neurons, and analyzed resulting (Hcrtr1Dbh-CKO) mice’, and their control littermates’ electrocortical response in several contexts of enhanced arousal. Under enforced wakefulness (EW), or after cage change (CC), Hcrtr1Dbh-CKO mice exhibited a weakened ability to lower infra-θ frequencies (1-7 Hz), and mount a robust, narrow-bandwidth, high-frequency θ rhythm (~8.5 Hz). A fast-γ (55-80 Hz) response, whose dynamics closely parallelled θ, also diminished, while β/slow-γ activity (15-45 Hz) increased. Furthermore, EW-associated locomotion was lower. Surprisingly, nestbuilding-associated wakefulness, inversely, featured enhanced θ and fast-γ activities. Thus HCRT-to-NA signalling may fine-tune arousal, up in alarming conditions, and down during self-motivated, goal-driven behaviors. Lastly, slow-wave-sleep following EW and CC, but not nestbuilding, was severely deficient in slow-δ waves (0.75-2.25 Hz), suggesting that HCRT-to-NA signalling regulates the slow-δ rebound characterizing sleep after stress-associated arousal.


2011 ◽  
Vol 278 (1717) ◽  
pp. 2419-2428 ◽  
Author(s):  
John A. Lesku ◽  
Alexei L. Vyssotski ◽  
Dolores Martinez-Gonzalez ◽  
Christiane Wilzeck ◽  
Niels C. Rattenborg

The function of the brain activity that defines slow wave sleep (SWS) and rapid eye movement (REM) sleep in mammals is unknown. During SWS, the level of electroencephalogram slow wave activity (SWA or 0.5–4.5 Hz power density) increases and decreases as a function of prior time spent awake and asleep, respectively. Such dynamics occur in response to waking brain use, as SWA increases locally in brain regions used more extensively during prior wakefulness. Thus, SWA is thought to reflect homeostatically regulated processes potentially tied to maintaining optimal brain functioning. Interestingly, birds also engage in SWS and REM sleep, a similarity that arose via convergent evolution, as sleeping reptiles and amphibians do not show similar brain activity. Although birds deprived of sleep show global increases in SWA during subsequent sleep, it is unclear whether avian sleep is likewise regulated locally. Here, we provide, to our knowledge, the first electrophysiological evidence for local sleep homeostasis in the avian brain. After staying awake watching David Attenborough's The Life of Birds with only one eye, SWA and the slope of slow waves (a purported marker of synaptic strength) increased only in the hyperpallium—a primary visual processing region—neurologically connected to the stimulated eye. Asymmetries were specific to the hyperpallium, as the non-visual mesopallium showed a symmetric increase in SWA and wave slope. Thus, hypotheses for the function of mammalian SWS that rely on local sleep homeostasis may apply also to birds.


1998 ◽  
Vol 275 (5) ◽  
pp. R1690-R1702 ◽  
Author(s):  
Michael E. Rashotte ◽  
Iuri F. Pastukhov ◽  
Eugene L. Poliakov ◽  
Ross P. Henderson

Fasting induces nocturnal hypothermia in pigeons. Slow-wave sleep (SWS) and paradoxical sleep (PS) are associated with reduced heat production in pigeons. The possibility that fasting-induced nocturnal hypothermia is related to increased SWS and PS was examined by comparing body temperature (Tb) and vigilance states when pigeons were fed and fasted. The results showed that when Tb is decreasing near the beginning of the dark phase, the percentage of total recording time (%TRT) spent in SWS and PS was elevated in fasting due to increased frequency of episodes and increased duration of PS episodes. When Tb was low during the middle segment of the dark phase, SWS was elevated in fasting due to increased episode duration. However, fasting did not alter PS, which increased in %TRT across the segment due to increased episode frequency. When Tb was rising during the final hours of dark, SWS remained elevated in fasting and %TRT in SWS and PS was relatively high. SWS and PS may promote the fasting pigeon’s entry into, and maintenance of, nocturnal hypothermia.


2020 ◽  
Vol 375 (1799) ◽  
pp. 20190234 ◽  
Author(s):  
Linlin Sun ◽  
Hang Zhou ◽  
Joseph Cichon ◽  
Guang Yang

Synaptic plasticity is important for learning and memory. With increasing evidence linking sleep states to changes in synaptic strength, an emerging view is that sleep promotes learning and memory by facilitating experience-induced synaptic plasticity. In this review, we summarize the recent progress on the function of sleep in regulating cortical synaptic plasticity. Specifically, we outline the electroencephalogram signatures of sleep states (e.g. slow-wave sleep, rapid eye movement sleep, spindles), sleep state-dependent changes in gene and synaptic protein expression, synaptic morphology, and neuronal and network activity. We highlight studies showing that post-experience sleep potentiates experience-induced synaptic changes and discuss the potential mechanisms that may link sleep-related brain activity to synaptic structural remodelling. We conclude that both synapse formation or strengthening and elimination or weakening occur across sleep. This sleep-dependent synaptic plasticity plays an important role in neuronal circuit refinement during development and after learning, while sleep disorders may contribute to or exacerbate the development of common neurological diseases. This article is part of the Theo Murphy meeting issue ‘Memory reactivation: replaying events past, present and future’.


SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A298-A298
Author(s):  
Augustus Kram Mendelsohn ◽  
Carolina Daffre ◽  
Katelyn Oliver ◽  
Jeehye Seo ◽  
Natasha Lasko ◽  
...  

Abstract Introduction Insomnia Disorder (ID) elevates risk of incident anxiety disorders and vice versa. We examined whether ID and poor sleep are associated with greater self-reported anxiety in persons with Generalized Anxiety Disorder (GAD). Methods Twenty-one participants with GAD and ID (GAD+/ID+) having Insomnia Severity Index (ISI) scores ≥ 13 (mean 17.8, SD 3.6) and 14 with GAD but not ID (GAD+/ID-) having ISI scores ≤ 12 (mean 6.4, SD 3.4) completed 14 days of actigraphy and sleep diaries as well as a night of ambulatory polysomnography (PSG) following an acclimation night. Participants completed the Pittsburgh Sleep Quality Index (PSQI), the State-Trait Inventory for Cognitive and Somatic Anxiety (STICSA-T/C, -T/S), the Ford Insomnia Response to Stress Test (FIRST), the Penn State Worry Questionnaire (PSWQ), and the Anxiety Sensitivity Index (ASI). Differences in self-reported anxiety (STICSA, ASI, PSWQ) between GAD+/ID+ and GAD+/ID- were analyzed using t-tests. Relationships of anxiety with retrospective (PSQI, FIRST, ISI), longitudinal (actigraphy, diaries) and physiological (PSG) sleep variables were analyzed using simple regression. Results GAD+/ID+ versus GAD+/ID- participants showed trends toward higher anxiety on the PSWQ (p=0.075), ASI (p=0.072) and STICSA-T/S (p=0.078). PSQI scores were positively associated with STICSA-T/S, (R=0.417, p=0.018, N=32). Greater insomnia reactivity (FIRST) was associated with increased worry on the PSWQ (R=0.352, p=0.044, N=33). STICSA-T/C was negatively associated with mean diary (R= -0.440, p=0.015, N=30) and actigraph (R= -0.517, p=0.01, N=24) total sleep time (TST). Actigraph mean TST trended toward lower PSWQ (R= -0.376, p=0.058, N=26) while actigraph mean sleep efficiency (SE) trended toward lesser STICSA-T/C (R= -0.397, p=0.058). Greater REM% was associated with greater STICSA-T/C (R=0.613, p=0.0005, N=28) and STICSA-T/S (R=0.516, p=0.005), a relationship also seen in GAD+/ID+ alone (p=0.03 and 0.015 respectively, N=16). Slow Wave Sleep% (SWS%) was not associated with lesser STICSA-T/S across both groups (p=0.14) but was so in GAD+/ID+ (R= -0.539, p=0.031, N=16). Conclusion GAD+/ID+ versus GAD+/ID-, show greater worry, anxiety sensitivity and somatic anxiety. In GAD, shorter and poorer quality sleep measured retrospectively or averaged longitudinally, as well as greater REM%, are associated with greater somatic and cognitive anxiety. Among those with ID, greater SWS% is associated with less somatic anxiety. Support (if any) R21MH115279, R01MH109638


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Li-Wei Ko ◽  
Cheng-Hua Su ◽  
Meng-Hsun Yang ◽  
Shen-Yi Liu ◽  
Tung-Ping Su

AbstractSleep quality is important to health and life quality. Lack of sleep can lead to a variety of health issues and reduce in daytime function. Recent study by Fultz et al. also indicated that sleep is crucial to brain metabolism. Delta power in sleep EEG often indicates good sleep quality while alpha power usually indicates sleep interruptions and poor sleep quality. Essential oil has been speculated to improve sleep quality. Previous studies also suggest essential oil aroma may affect human brain activity when applied awake. However, those studies were often not blinded, which makes the effectiveness and mechanism of aroma a heavily debated topic. In this study, we aim to explore the effect of essential oil aroma on human sleep quality and sleep EEG in a single-blinded setup. The aroma was released when the participants are asleep, which kept the influence of psychological expectation to the minimum. We recruited nine young, healthy participants with regular lifestyle and no sleep problem. All participants reported better sleep quality and more daytime vigorous after exposing to lavender aroma in sleep. We also observed that upon lavender aroma releases, alpha wave in wake stage was reduced while delta wave in slow-wave sleep (SWS) was increased. Lastly, we found that lavender oil promote occurrence of SWS. Overall, our study results show that essential oil aroma can be used to promote both subjective and objective sleep quality in healthy human subjects. This makes aroma intervention a potential solution for poor sleep quality and insomnia.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sophie Bagur ◽  
Julie M. Lefort ◽  
Marie M. Lacroix ◽  
Gaëtan de Lavilléon ◽  
Cyril Herry ◽  
...  

AbstractBrain–body interactions are thought to be essential in emotions but their physiological basis remains poorly understood. In mice, regular 4 Hz breathing appears during freezing after cue-fear conditioning. Here we show that the olfactory bulb (OB) transmits this rhythm to the dorsomedial prefrontal cortex (dmPFC) where it organizes neural activity. Reduction of the respiratory-related 4 Hz oscillation, via bulbectomy or optogenetic perturbation of the OB, reduces freezing. Behavioural modelling shows that this is due to a specific reduction in freezing maintenance without impacting its initiation, thus dissociating these two phenomena. dmPFC LFP and firing patterns support the region’s specific function in freezing maintenance. In particular, population analysis reveals that network activity tracks 4 Hz power dynamics during freezing and reaches a stable state at 4 Hz peak that lasts until freezing termination. These results provide a potential mechanism and a functional role for bodily feedback in emotions and therefore shed light on the historical James–Cannon debate.


2021 ◽  
Author(s):  
Feng Han ◽  
Gregory L. Brown ◽  
Yalin Zhu ◽  
Aaron E. Belkin‐Rosen ◽  
Mechelle M. Lewis ◽  
...  

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Jizheng Zhao ◽  
Dardo Tomasi ◽  
Corinde E. Wiers ◽  
Ehsan Shokri-Kojori ◽  
Şükrü B. Demiral ◽  
...  

Negative urgency (NU) and positive urgency (PU) are implicated in several high-risk behaviors, such as eating disorders, substance use disorders, and nonsuicidal self-injury behavior. The current study aimed to explore the possible link between trait of urgency and brain activity at rest. We assessed the amplitude of low-frequency fluctuations (ALFF) of the resting-state functional magnetic resonance imaging (fMRI) signal in 85 healthy volunteers. Trait urgency measures were related to ALFF in the lateral orbitofrontal cortex, dorsolateral prefrontal cortex, ventral and dorsal medial frontal cortex, anterior cingulate, and posterior cingulate cortex/precuneus. In addition, trait urgency measures showed significant correlations with the functional connectivity of the posterior cingulate cortex/precuneus seed with the thalamus and midbrain region. These findings suggest an association between intrinsic brain activity and impulsive behaviors in healthy humans.


2010 ◽  
Vol 107 (5) ◽  
pp. 2265-2270 ◽  
Author(s):  
Zachary M. Weil ◽  
Qiuyu Zhang ◽  
Allison Hornung ◽  
David Blizard ◽  
Donald W. Pfaff

Although there is an extensive amount known about specific sensory and motor functions of the vertebrate brain, less is understood about the regulation of global brain states. We have recently proposed that a function termed generalized arousal (Ag) serves as the most elemental driving force in the nervous system, responsible for the initial activation of all behavioral responses. An animal with increased generalized CNS arousal is characterized by greater motor activity, increased responsivity to sensory stimuli, and greater emotional lability. Implicit in this theory was the prediction that increases in generalized arousal would augment specific motivated behaviors that depend on arousal. Here, we address the idea directly by testing two lines of mice bred for high or low levels of generalized arousal and assessing their responses in tests of specific forms of behavioral arousal, sex and anxiety/exploration. We report that animals selected for differential generalized arousal exhibit marked increases in sensory, motor, and emotional reactivity in our arousal assay. Furthermore, male mice selected for high levels of generalized arousal were excitable and showed more incomplete mounts before the first intromission (IN), but having achieved that IN, they exhibited far fewer IN before ejaculating, as well as ejaculating much sooner after the first IN, thus indicating a high level of sexual arousal. Additionally, high-arousal animals of both sexes exhibited greater levels of anxiety-like behaviors and reduced exploratory behavior in the elevated plus maze and light-dark box tasks. Taken together, these data illustrate the impact of Ag on motivated behaviors.


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