Noradrenergic<i>locus coeruleus</i>activity functionally partitions NREM sleep to gatekeep the NREM-REM sleep cycle

Osorio-Forero, Alejandro; Foustoukos, Georgios; Cardis, Romain; Cherrad, Najma; Devenoges, Christiane; Fernandez, Laura M. J.; Lüthi, Anita

doi:10.1101/2023.05.20.541586

Cited by 25 publications

(6 citation statements)

References 103 publications

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“…As soon as a REMs episode was detected, a small vibrating motor attached to the animal’s head was turned on to terminate REMs by briefly awakening the animal ( Fig. 3A, S5A ) (Cardis et al, 2021; Osorio-Forero et al, 2023). Compared with the baseline recordings from the same mice during the same circadian time, we found that 6 h of REMs restriction (ZT 1.5-7.5) significantly reduced the amount of REMs and duration of REMs episodes, while increasing their frequency ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…We employed an automatic REMs detection algorithm (Weber et al, 2015, 2018; Stucynski et al, 2022; Schott et al, 2023) and used a small vibrating motor to terminate/restrict REMs (Cardis et al, 2021; Osorio-Forero et al, 2023) (https://github.com/luthilab/IntanLuthiLab). A small vibrating motor (DC 3V Mini Vibration Motor, diameter: 10mm, thickness: 3mm, BOJACK) with a soldered lobster claw clasp was attached to a small wire hook secured in the dental cement of each mouse head.…”

Section: Methodsmentioning

confidence: 99%

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Homeostatic regulation of REM sleep by the preoptic area of the hypothalamus

Maurer,

Lin,

Jin

et al. 2023

Preprint

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Rapid-eye-movement sleep (REMs) is characterized by activated electroencephalogram (EEG) and muscle atonia, accompanied by vivid dreams. REMs is homeostatically regulated, ensuring that any loss of REMs is compensated by a subsequent increase in its amount. However, the neural mechanisms underlying the homeostatic control of REMs are largely unknown. Here, we show that GABAergic neurons in the preoptic area of the hypothalamus projecting to the tuberomammillary nucleus (POAGAD2→TMN neurons) are crucial for the homeostatic regulation of REMs. POAGAD2→TMN neurons are most active during REMs, and inhibiting them specifically decreases REMs. REMs restriction leads to an increased number and amplitude of calcium transients in POAGAD2→TMN neurons, reflecting the accumulation of REMs pressure. Inhibiting POAGAD2→TMN neurons during REMs restriction blocked the subsequent rebound of REMs. Our findings reveal a hypothalamic circuit whose activity mirrors the buildup of homeostatic REMs pressure during restriction and that is required for the ensuing rebound in REMs.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Homeostatic regulation of REM sleep by the preoptic area of the hypothalamus

Maurer,

Lin,

Jin

et al. 2023

Preprint

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“…Such algorithms could also be adapted for use in the clinical setting. Animal studies have recently provided interesting EEG readouts of arousal system activity (for instance of the locus coeruleus), which appear to hold true for humans (Kjaerby et al, 2022;Lecci et al, 2017;Osorio-Forero et al, 2023). Translational studies of this type will be crucial to better understand which networks and neuro-modulatory systems are involved in sleep perception and to plan studies evaluating the effect of specific pharmacological manipulations on subjective sleep quality.…”

Section: Within-subject Contrast and Correlations (Serial Awakening P...mentioning

confidence: 99%

Reconsidering sleep perception in insomnia: from misperception to mismeasurement

Stephan,

Siclari

2023

Journal of Sleep Research

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SummarySo‐called ‘sleep misperception’ refers to a phenomenon in which individuals have the impression of sleeping little or not at all despite normal objective measures of sleep. It is unknown whether this subjective–objective mismatch truly reflects an abnormal perception of sleep, or whether it results from the inability of standard sleep recording techniques to capture ‘wake‐like’ brain activity patterns that could account for feeling awake during sleep. Here, we systematically reviewed studies reporting sleep macro‐ and microstructural, metabolic, and mental correlates of sleep (mis)perception. Our findings suggest that most individuals tend to accurately estimate their sleep duration measured with polysomnography (PSG). In good sleepers, feeling awake during sleep is the rule at sleep onset, remains frequent in the first non‐rapid eye movement sleep cycle and almost never occurs in rapid eye movement (REM) sleep. In contrast, there are patients with insomnia who consistently underestimate their sleep duration, regardless of how long they sleep. Unlike good sleepers, they continue to feel awake after the first sleep cycle and importantly, during REM sleep. Their mental activity during sleep is also more thought‐like. Initial studies based on standard PSG parameters largely failed to show consistent differences in sleep macrostructure between these patients and controls. However, recent studies assessing sleep with more refined techniques have revealed that these patients show metabolic and microstructural electroencephalography changes that likely reflect a shift towards greater cortical activation during sleep and correlate with feeling awake. We discuss the significance of these correlates and conclude with open questions and possible ways to address them.

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“…As soon as a REMs episode was detected, a small vibrating motor attached to the animal's head was turned on to terminate REMs by briefly awakening the animal (Fig. 3A , S4A ) (Cardis et al, 2021 ;Osorio-Forero et al, 2023 ). Compared with the baseline recordings from the same mice during the same circadian time, we found that 6 h of REMs restriction (ZT 1.5-7.5) significantly reduced the amount of REMs and duration of REMs episodes, while increasing their frequency (Fig.…”

Section: Poa Gad2 →Tmn Neurons Exhibit An Increased Number Of Calcium...mentioning

confidence: 99%

“…We employed an automatic REMs detection algorithm (Weber et al, 2015(Weber et al, , 2018Stucynski et al, 2022 ;Schott et al, 2023 ) and used a small vibrating motor to terminate/restrict REMs (Cardis et al, 2021 ;Osorio-Forero et al, 2023 ) (https://github.com/luthilab/IntanLuthiLab ). A small vibrating motor (DC 3V Mini Vibration Motor, diameter: 10mm, thickness: 3mm, BOJACK) with a soldered lobster claw clasp was attached to a small wire hook secured in the dental cement of each mouse head.…”

Section: Rems Restrictionmentioning

confidence: 99%

Homeostatic regulation of REM sleep by the preoptic area of the hypothalamus

Maurer,

Lin,

Jin

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

Rapid-eye-movement sleep (REMs) is characterized by activated electroencephalogram (EEG) and muscle atonia, accompanied by vivid dreams. REMs is homeostatically regulated, ensuring that any loss of REMs is compensated by a subsequent increase in its amount. However, the neural mechanisms underlying the homeostatic control of REMs are largely unknown. Here, we show that GABAergic neurons in the preoptic area of the hypothalamus projecting to the tuberomammillary nucleus (POA GAD2 →TMN neurons) are crucial for the homeostatic regulation of REMs. POA GAD2 →TMN neurons are most active during REMs, and inhibiting them specifically decreases REMs. REMs restriction leads to an increased number and amplitude of calcium transients in POA GAD2 →TMN neurons, reflecting the accumulation of REMs pressure. Inhibiting POA GAD2 →TMN neurons during REMs restriction blocked the subsequent rebound of REMs. Our findings reveal a hypothalamic circuit whose activity mirrors the buildup of homeostatic REMs pressure during restriction and that is required for the ensuing rebound in REMs.

show abstract

Noradrenergiclocus coeruleusactivity functionally partitions NREM sleep to gatekeep the NREM-REM sleep cycle

Cited by 25 publications

References 103 publications

Homeostatic regulation of REM sleep by the preoptic area of the hypothalamus

Homeostatic regulation of REM sleep by the preoptic area of the hypothalamus

Reconsidering sleep perception in insomnia: from misperception to mismeasurement

Homeostatic regulation of REM sleep by the preoptic area of the hypothalamus

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