A Hypothalamic Switch for REM and Non-REM Sleep

Chen, Kai Siang; Xu, Min; Zhang, Zhe; Chang, Wei Cheng; Gaj, Thomas; Schaffer, David V.; Dan, Yang

doi:10.1016/j.neuron.2018.02.005

Cited by 121 publications

(88 citation statements)

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“…Microendoscopy has been used to image the activity of various phenotypes of brain neurons during quiet waking and sleep (Weber et al, 2015(Weber et al, , 2018Cox et al, 2016;Chung et al, 2017;Chen et al, 2018). We took advantage of the versatility of the miniscope by also imaging the same neurons while the mice were exploring novel objects and discovered that 70% of the MCH neurons that were active in REM sleep were also active during the exploration of novel objects.…”

Section: Discussionmentioning

confidence: 99%

Dynamic Network Activation of Hypothalamic MCH Neurons in REM Sleep and Exploratory Behavior

et al. 2019

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Most brain neurons are active in waking, but hypothalamic neurons that synthesize the neuropeptide melanin-concentrating hormone (MCH) are claimed to be active only during sleep, particularly rapid eye movement (REM) sleep. Here we use deep-brain imaging to identify changes in fluorescence of the genetically encoded calcium (Ca 2ϩ ) indicator GCaMP6 in individual hypothalamic neurons that contain MCH. An in vitro electrophysiology study determined a strong relationship between depolarization and Ca 2ϩ fluorescence in MCH neurons. In 10 freely behaving MCH-cre mice (male and female), the highest fluorescence occurred in all recorded neurons (n ϭ 106) in REM sleep relative to quiet waking or non-REM sleep. Unexpectedly, 70% of the MCH neurons had strong fluorescence activity when the mice explored novel objects. Spatial and temporal mapping of the change in fluorescence between pairs of MCH neurons revealed dynamic activation of MCH neurons during REM sleep and activation of a subset of the same neurons during exploratory behavior. Functional network activity maps will facilitate comparisons of not only single-neuron activity, but also network responses in different conditions and disease.

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Section: Discussionmentioning

confidence: 99%

Dynamic Network Activation of Hypothalamic MCH Neurons in REM Sleep and Exploratory Behavior

et al. 2019

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“…A separate GABAergic population in the nearby zona incerta (ZI), which expresses the LIM homeodomain factor Lhx6, is activated by sleep pressure, and its chemogenetic activation promotes REM and NREM sleep (Liu et al 2017). In the dorsomedial hypothalamic nucleus (DMH), the subset of galanin-expressing GABAergic neurons that projects to the POA is preferentially active during NREM sleep, and its optogenetic activation promotes NREM sleep while suppressing REM sleep (Chen et al 2018).…”

Section: Ne42ch02_danmentioning

confidence: 99%

“…As summarized in Figure 2b, these include MCH-expressing neurons in the lateral hypothalamus (Hassani et al 2009b, Jego et al 2013, Konadhode et al 2013, Tsunematsu et al 2014, Lhx6-expressing ZI neurons (Liu et al 2017), and CCK-or CRH-expressing POA neurons (Chung et al 2017). In the DMH, on the other hand, the galanin-expressing neurons projecting to the raphe pallidus are preferentially active during REM sleep, and their optogenetic activation promotes REM sleep at the expense of NREM sleep (Chen et al 2018) (Figure 2c).…”

Section: Medullary Rem Zonesmentioning

confidence: 99%

“…GABAergic neurons in the vlPAG strongly promote NREM sleep by suppressing both wakefulness and REM sleep, although their firing rates are higher during wakefulness than NREM sleep (Weber et al 2015(Weber et al , 2018. Galanin-expressing neurons in the DMH that project to the POA are both NREM active and NREM promoting (Chen et al 2018). Several other populations have been shown to specifically promote NREM sleep, including the POA neurons activated by the α2 adrenergic receptor agonist dexmedetomidine (Zhang et al 2015), TAC1-and PDYN-expressing GABAergic neurons in the lateral POA (Chung et al 2017), warm-sensing neurons in the median/ medial POA (Harding et al 2018), a subset of glutamatergic neurons in the pontine tegmentum (Hayashi et al 2015), and adenosine A2A receptor-expressing neurons in the dorsal and ventral striatum (Oishi et al 2017, Yuan et al 2017.…”

Section: Wwwannualreviewsorg • Arousal-action Circuit 37mentioning

confidence: 99%

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A Motor Theory of Sleep-Wake Control: Arousal-Action Circuit

Liu

Dan

2019

Annu. Rev. Neurosci.

Self Cite

144

141

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Wakefulness, rapid eye movement (REM) sleep, and non–rapid eye movement (NREM) sleep are characterized by distinct electroencephalogram (EEG), electromyogram (EMG), and autonomic profiles. The circuit mechanism coordinating these changes during sleep-wake transitions remains poorly understood. The past few years have witnessed rapid progress in the identification of REM and NREM sleep neurons, which constitute highly distributed networks spanning the forebrain, midbrain, and hindbrain. Here we propose an arousal-action circuit for sleep-wake control in which wakefulness is supported by separate arousal and action neurons, while REM and NREM sleep neurons are part of the central somatic and autonomic motor circuits. This model is well supported by the currently known sleep and wake neurons. It can also account for the EEG, EMG, and autonomic profiles of wake, REM, and NREM states and several key features of their transitions. The intimate association between the sleep and autonomic/somatic motor control circuits suggests that a primary function of sleep is to suppress motor activity.

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“…An alternative view hypothesizes that sleep is imposed upon the brain by the activity of centrally acting, circadian-and/or homeostatic-sensitive sleep-promoting neurons. Numerous classes of neuronal subpopulations in both Drosophila and mammals have been identified that are capable of driving sleep and wake when stimulated by opto-and chemogenetic approaches (Chen et al, 2018;Chung et al, 2017;Donlea et al, 2014;Donlea et al, 2018;Kroeger et al, 2018;Seidner et al, 2015;Xu et al, 2015). In addition, focal lesions of some brain nuclei, for example the mammalian ventro-lateral preoptic area (VLPO), can cause severe insomnia (Lu et al, 2000), demonstrating that a loss of a small number of critical neurons can have a large effect on sleep.…”

Section: Introductionmentioning

confidence: 99%

The neuropeptide Galanin is required for homeostatic rebound sleep following increased neuronal activity

Reichert

Arocas

Rihel

2018

Preprint

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Sleep pressure homeostatically increases during wake and dissipates during sleep, but the molecular signals and neuronal substrates that measure homeostatic sleep pressure remain poorly understood. We present a pharmacological assay in larval zebrafish that generates acute, short-term increases in wakefulness followed by sustained rebound sleep after washout. The intensity of global neuronal activity during drug-induced wakefulness predicted the amount of subsequent rebound sleep. Whole brain mapping with the neuronal activity marker phosphorylated extracellular signal-regulated kinase (pERK) identified preoptic Galanin-expressing neurons as selectively active during rebound sleep, and the relative induction of galanin transcripts was predictive of total rebound sleep time. Galanin is required for sleep homeostasis, as galanin mutants almost completely lacked rebound sleep following both pharmacologically induced neuronal activity and physical sleep deprivation. These results suggest that Galanin plays a key role in responding to sleep pressure signals derived from neuronal activity and functions as an output arm of the vertebrate sleep homeostat.

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A Hypothalamic Switch for REM and Non-REM Sleep

Cited by 121 publications

References 50 publications

Dynamic Network Activation of Hypothalamic MCH Neurons in REM Sleep and Exploratory Behavior

Dynamic Network Activation of Hypothalamic MCH Neurons in REM Sleep and Exploratory Behavior

A Motor Theory of Sleep-Wake Control: Arousal-Action Circuit

The neuropeptide Galanin is required for homeostatic rebound sleep following increased neuronal activity

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