Genetic and neuronal regulation of sleep by neuropeptide VF

Lee, Dan A.; Andreev, Andrey; Truong, Thai V.; Chen, Audrey; Hill, Andrew J.; Oikonomou, Grigorios; Pham, Uyen; Hong, Young; Tran, Steven; Glass, L R; Sapin, Viveca; Engle, Jae; Fraser, Scott E.; Prober, David A.

doi:10.7554/elife.25727

Cited by 57 publications

(101 citation statements)

References 124 publications

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“…Consistent with these findings, the kcnh4a potassium channel genes act in hcrt neurons to regulate their activity, with kcnh4a knockout resulting in a 15% sleep reduction [94]. Loss of function of the npvf neuropeptide gene also causes hyperactivity and reduces sleep by 10% [95]. Mutation of the melatonin receptor gene aanat2 in zebrafish reduces night sleep in the presence of light-dark cycles by about 50%.…”

Section: Genetically Removing Sleep In Model Systems: Zebrafishmentioning

confidence: 67%

Genetic sleep deprivation: using sleep mutants to study sleep functions

Bringmann

2019

EMBO Reports

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Sleep is a fundamental conserved physiological state in animals and humans. It may serve multiple functions, ranging from energy conservation to higher brain operation. Understanding sleep functions and the underlying mechanisms requires the study of sleeplessness and its consequences. The traditional approach to remove sleep is sleep deprivation ( SD ) by sensory stimulation. However, stimulation‐induced SD can be stressful and can cause non‐specific side effects. An emerging alternative method is “genetic SD ”, which removes sleep using genetics or optogenetics. Sleep requires sleep‐active neurons and their regulators. Thus, genetic impairment of sleep circuits might lead to more specific and comprehensive sleep loss. Here, I discuss the advantages and limits of genetic SD in key genetic sleep model animals: rodents, zebrafish, fruit flies and roundworms, and how the study of genetic SD alters our view of sleep functions. Genetic SD typically causes less severe phenotypes compared with stimulation‐induced SD , suggesting that sensory stimulation‐induced SD may have overestimated the role of sleep, calling for a re‐investigation of sleep functions.

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Section: Genetically Removing Sleep In Model Systems: Zebrafishmentioning

confidence: 67%

Genetic sleep deprivation: using sleep mutants to study sleep functions

Bringmann

2019

EMBO Reports

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“…To explore whether the NPVF system may promote sleep via the RN, we first performed a detailed histological analysis of these populations using Tg(npvf:eGFP) (Lee et al, 2017) and Tg(npvf:KalTA4); Tg(UAS:nfsb-mCherry) (Agetsuma et al, 2010; Lee et al, 2017) animals, which specifically label npvf -expressing neurons. As previously described (Lee et al, 2017), the soma of npvf -expressing neurons are present exclusively in the dorsomedial hypothalamus at 6 days post-fertilization (dpf) ( Figure 1A,B,D ).…”

Section: Resultsmentioning

confidence: 99%

“…One candidate neuronal population expresses the sleep-promoting neuropeptide VF (NPVF) in ∼25 neurons in the larval zebrafish hypothalamus (Lee et al, 2017). Overexpression of npvf or stimulation of npvf -expressing neurons results in increased sleep, whereas pharmacological inhibition of NPVF signaling or ablation of npvf -expressing neurons results in reduced sleep (Lee et al, 2017). While it is unknown how the NPVF system promotes sleep, these neurons densely innervate a region of the hindbrain that is consistent with the location of the RN (Lee et al, 2017; Madelaine et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

“…Overexpression of npvf or stimulation of npvf -expressing neurons results in increased sleep, whereas pharmacological inhibition of NPVF signaling or ablation of npvf -expressing neurons results in reduced sleep (Lee et al, 2017). While it is unknown how the NPVF system promotes sleep, these neurons densely innervate a region of the hindbrain that is consistent with the location of the RN (Lee et al, 2017; Madelaine et al, 2017). Because perturbations of the NPVF system and RN have similar effects on sleep, and processes of npvf -expressing neurons are found near the RN, we hypothesized that the NPVF system promotes sleep via the RN.…”

Section: Introductionmentioning

confidence: 99%

“… ABSTRACTAlthough several sleep-regulating neurons have been identified, little is known about how they interact with each other for sleep/wake control. We previously identified neuropeptide VF (NPVF) and the hypothalamic neurons that produce it as a sleep-promoting system (Lee et al, 2017). Here we use zebrafish to describe a neural circuit in which neuropeptide VF ( npvf )-expressing neurons control sleep via the serotonergic raphe nuclei (RN), a hindbrain structure that promotes sleep in both diurnal zebrafish and nocturnal mice.…”

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confidence: 99%

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Neuropeptide VF neurons promote sleep via the serotonergic raphe

Lee

Oikonomou

Cammidge

et al. 2019

Preprint

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15Although several sleep-regulating neurons have been identified, little is known about how they 16 interact with each other for sleep/wake control. We previously identified neuropeptide VF (NPVF) 17 and the hypothalamic neurons that produce it as a sleep-promoting system (Lee et al., 2017). 18Here we use zebrafish to describe a neural circuit in which neuropeptide VF (npvf)-expressing 19 neurons control sleep via the serotonergic raphe nuclei (RN), a hindbrain structure that promotes 20 sleep in both diurnal zebrafish and nocturnal mice. Using genetic labeling and calcium imaging, 21we show that npvf-expressing neurons innervate and activate serotonergic RN neurons. We 22 additionally demonstrate that optogenetic stimulation of npvf-expressing neurons induces sleep 23 in a manner that requires NPVF and is abolished when the RN are ablated or lack serotonin. 24Finally, genetic epistasis demonstrates that NPVF acts upstream of serotonin in the RN to 25 maintain normal sleep levels. These findings reveal a novel hypothalamic-hindbrain circuit for 26 sleep/wake control. 28While several sleep-and wake-promoting neuronal populations have been identified (reviewed in 30 (Bringmann, 2018; Liu and Dan, 2019; Saper and Fuller, 2017; Scammell et al., 2017)), 31 characterizing and understanding the functional and hierarchical relationships between these 32 populations is essential for understanding how the brain regulates sleep and wake states 33 (Oikonomou and Prober, 2017). Recent evidence from zebrafish and mice demonstrate that the 34 serotonergic raphe nuclei (RN) are critical for the initiation and maintenance of sleep (Oikonomou 35 et al., 2019), in contrast with previous models suggesting a wake-promoting role for the RN that 36 were largely based on their wake-active nature (Saper and Fuller, 2017; Scammell et al., 2017; 37Weber and Dan, 2016). In zebrafish, mutation of tryptophan hydroxylase 2 (tph2), which is 38 required for serotonin (5-HT) synthesis in the RN, results in reduced sleep, sleep depth, and 39 homeostatic response to sleep deprivation (Oikonomou et al., 2019). Pharmacological inhibition 40 of 5-HT synthesis or ablation of the RN also results in reduced sleep. Consistent with a sleep-41 promoting role for the raphe, optogenetic stimulation of raphe neurons results in increased sleep.42 Similarly, in mice, ablation of the RN results in increased wakefulness and an impaired 43 homeostatic response to sleep deprivation, whereas tonic optogenetic stimulation of the RN at a 44 rate similar to their baseline pattern of activity induces NREM sleep. These complementary results 45 in zebrafish and mice (Oikonomou et al., 2019), along with classical ablation and pharmacological 46 studies (Ursin, 2008), indicate an evolutionarily conserved role for the serotonergic system in 47 promoting vertebrate sleep. However, it is unclear how the RN are themselves regulated to 48 promote sleep. 50Trans-synaptic retrograde viral tracing studies have identified substantial inputs to the RN from 51 hypothalamic ...

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Methods to Study Sleep in Zebrafish

Tran

Prober

2022

Circadian Clocks

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Genetic and neuronal regulation of sleep by neuropeptide VF

Cited by 57 publications

References 124 publications

Genetic sleep deprivation: using sleep mutants to study sleep functions

Genetic sleep deprivation: using sleep mutants to study sleep functions

Neuropeptide VF neurons promote sleep via the serotonergic raphe

Methods to Study Sleep in Zebrafish

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