Sleep homeostasis regulated by 5HT2b receptor in a small subset of neurons in the dorsal fan-shaped body of drosophila

Qian, Yongjun; Cao, Yue; Deng, Bowen; Yang, Guang; Li, Jiayun; Xu, Rui; Zhang, Dandan; Huang, Juan; Rao, Yi

doi:10.7554/elife.26519

Cited by 100 publications

(166 citation statements)

References 101 publications

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“…We and others recently addressed this controversy in both mammals and zebrafish by providing both gain- and loss-of-function evidence using genetic, pharmacological, optogenetic and chemogenetic approaches to demonstrate that the serotonergic RN promote sleep (Oikonomou et al, 2019; Venner et al, 2019). This finding agrees with invertebrate studies which showed that 5-HT signaling promotes sleep in Drosophila (Qian et al, 2017; Yuan et al, 2006). However, while 5-HT plays an evolutionarily conserved role in promoting sleep, the neuronal mechanism that acts upon serotonergic neurons to promote sleep was unknown.…”

Section: Discussionsupporting

confidence: 92%

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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Section: Discussionsupporting

confidence: 92%

Neuropeptide VF neurons promote sleep via the serotonergic raphe

Lee

Oikonomou

Cammidge

et al. 2019

Preprint

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“…including courtship drive. [88][89][90][91][92] Serotonin is involved in many behaviors such as feeding, which directly affects longevity, 93 locomotion, 94 mating and courtship, 95 aggression, 96 and has modulatory effects on sleep-wake cycles, 97 and memory. 87,88 Some studies report decrease in dopaminergic cells viability with age, 78 while other do not.…”

Section: Neural Agingmentioning

confidence: 99%

“…88 However, the function of those dopaminergic cells, and the behaviors modulated by DA, might still be affected by aging. [88][89][90][91][92] Serotonin is involved in many behaviors such as feeding, which directly affects longevity, 93 locomotion, 94 mating and courtship, 95 aggression, 96 and has modulatory effects on sleep-wake cycles, 97 and memory. 98 Despite its wide-range involvement in behavior, and the fact that serotonin modulates the response to physical stress, 99 little attention has been given to studying the role of serotonin in aging.…”

Section: Neural Agingmentioning

confidence: 99%

Social behavior and aging: A fly model

Brenman-Suttner

Yost

Frame

et al. 2019

Genes Brain and Behavior

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The field of behavioral genetics has recently begun to explore the effect of age on social behaviors. Such studies are particularly important, as certain neuropsychiatric disorders with abnormal social interactions, like autism and schizophrenia, have been linked to older parents. Appropriate social interaction can also have a positive impact on longevity, and is associated with successful aging in humans. Currently, there are few genetic models for understanding the effect of aging on social behavior and its potential transgenerational inheritance. The fly is emerging as a powerful model for identifying the basic molecular mechanisms underlying neurological and neuropsychiatric disorders. In this review, we discuss these recent advancements, with a focus on how studies in Drosophila melanogaster have provided insight into the effect of aging on aspects of social behavior, including across generations.

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“…We show that circuits required for formation of alcohol preference shift from population-level dopaminergic encoding to two microcircuits comprising of interconnected dopaminergic, glutamatergic, and cholinergic neurons. These circuits converge onto the fan-shaped body (FSB), a higherorder brain center implicated in arousal and modulating behavioral response (Liu, Seiler et al 2006, Weir, Schnell et al 2014, Weir and Dickinson 2015, Pimentel, Donlea et al 2016, Qian, Cao et al 2017, Donlea, Pimentel et al 2018, Hu, Peng et al 2018, Troup, Yap et al 2018. Our results, therefore, provide an in vivo circuit framework for how drugs of abuse temporally regulate acquisition and expression of sensory memories, which ultimately results in a shift in behavioral response from malleable to inflexible.…”

Section: Introductionmentioning

confidence: 72%

Circuits that encode and predict alcohol associated preference

Scaplen

Talay

Salamon

et al. 2019

Preprint

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Substance use disorders are chronic relapsing disorders often impelled by enduring memories and persistent cravings. Alcohol, as well as other addictive substances, remolds neural circuits important for memory to establish obstinate preference despite aversive consequences. How pertinent circuits are selected and shaped to result in these unchanging, inflexible memories is unclear. Using neurogenetic tools available in Drosophila melanogaster we define how circuits required for alcohol associated preference shift from population level dopaminergic activation to select dopamine neurons that predict behavioral choice. During memory expression, these dopamine neurons directly, and indirectly via the mushroom body (MB), modulate the activity of interconnected glutamatergic and cholinergic output neurons. Transsynaptic tracing of these output neurons revealed at least two regions of convergence: 1) a center of memory consolidation within the MB implicated in arousal, and 2) a structure outside the MB implicated in integration of naïve and learned responses. These findings provide a circuit framework through which dopamine neuron activation shifts from reward delivery to cue onset, and provides insight into the inflexible, maladaptive nature of alcohol associated memories.

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Sleep homeostasis regulated by 5HT2b receptor in a small subset of neurons in the dorsal fan-shaped body of drosophila

Cited by 100 publications

References 101 publications

Neuropeptide VF neurons promote sleep via the serotonergic raphe

Neuropeptide VF neurons promote sleep via the serotonergic raphe

Social behavior and aging: A fly model

Circuits that encode and predict alcohol associated preference

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