Optogenetic activation of DRN 5-HT neurons induced active wakefulness, not quiet wakefulness

Moriya, Rika; Kanamaru, Mitsuko; Naoki, Okuma; Yoshikawa, Akira; Tanaka, Kenji F.; Hokari, Satoshi; Ohshima, Yasuyoshi; Yamanaka, Akihiro; Honma, Motoyasu; Onimaru, Hiroshi; Kikuchi, Toshiaki; Izumizaki, Masahiko

doi:10.1016/j.brainresbull.2021.09.019

Cited by 17 publications

(13 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The DRN regulates numerous physiological functions by integrating inputs from the whole brain ( Okaty et al, 2019 ). Optogenetic or chemogenetic activation of DRN 5–HT neurons can induce active wakefulness ( Moriya et al, 2021 ) and increase depressive-like behavior ( Teissier et al, 2015 ), but it halts spontaneous activity ( Correia et al, 2017 ). On the contrary, 5-HT deficiency in the adult brain increases locomotor activity without inducing anxiety-like behavior ( Whitney et al, 2016 ).…”

Section: Discussionmentioning

confidence: 99%

“…Among them, 5-HT neurons make up around half of the total neuronal population in the DRN ( Descarries et al, 1982 ). DRN 5–HT neurons have multiple physiological functions, including stress and anxiety-like behavior ( Hale et al, 2012 ; Ohmura et al, 2014 ), mood ( Cools et al, 2008 ), patience and impulsivity ( Miyazaki et al, 2012 ), locomotor activity ( Gately et al, 1985 ; Eagle et al, 2009 ; Correia et al, 2017 ), and sleep/wakefulness regulation ( Monti, 2010a , b ; Moriya et al, 2021 ). GABAergic neurons are another cell type in the DRN, and they regulate 5-HT neuron activity through a feedforward inhibition ( Geddes et al, 2016 ; Huang et al, 2017 ; Zhou et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Functional Interaction Between GABAergic Neurons in the Ventral Tegmental Area and Serotonergic Neurons in the Dorsal Raphe Nucleus

et al. 2022

Self Cite

View full text Add to dashboard Cite

GABAergic neurons in the ventral tegmental area (VTA) have brain-wide projections and are involved in multiple behavioral and physiological functions. Here, we revealed the responsiveness of Gad67+ neurons in VTA (VTAGad67+) to various neurotransmitters involved in the regulation of sleep/wakefulness by slice patch clamp recording. Among the substances tested, a cholinergic agonist activated, but serotonin, dopamine and histamine inhibited these neurons. Dense VTAGad67+ neuronal projections were observed in brain areas regulating sleep/wakefulness, including the central amygdala (CeA), dorsal raphe nucleus (DRN), and locus coeruleus (LC). Using a combination of electrophysiology and optogenetic studies, we showed that VTAGad67+ neurons inhibited all neurons recorded in the DRN, but did not inhibit randomly recorded neurons in the CeA and LC. Further examination revealed that the serotonergic neurons in the DRN (DRN5–HT) were monosynaptically innervated and inhibited by VTAGad67+ neurons. All recorded DRN5–HT neurons received inhibitory input from VTAGad67+ neurons, while only one quarter of them received inhibitory input from local GABAergic neurons. Gad67+ neurons in the DRN (DRNGad67+) also received monosynaptic inhibitory input from VTAGad67+ neurons. Taken together, we found that VTAGad67+ neurons were integrated in many inputs, and their output inhibits DRN5–HT neurons, which may regulate physiological functions including sleep/wakefulness.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Functional Interaction Between GABAergic Neurons in the Ventral Tegmental Area and Serotonergic Neurons in the Dorsal Raphe Nucleus

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…Furthermore, Moriya, Kanamaru, Okuma et al 51 showed that both QW and NREM sleep share similar patterns of acetylcholine and glutamate signalling in the hippocampus, and that experimental interventions can independently impact active wakefulness without influencing quiet wakefulness.…”

Section: Discussionmentioning

confidence: 99%

“…Within the preclinical literature concerning the quiet wake state, various titles are used (i.e., resting wake, awake quiescence, attentive wake) and defining criteria are typically vague, differing within and between species. However, most definitions converge on the fundamental criterion of 'relaxed' wakefulness with no locomotion [48][49][50][51] . Recently, studies using PSG-based definitions demonstrated important neurobiological differences between active and quiet wakefulness: beta activity (15-35 Hz)-during QW but not AW-couples with slow-wave activity to reveal homeostatic sleep drive 52 .…”

Section: Quiet Wakefulness and Mechanismsmentioning

confidence: 99%

Quiet wakefulness: The influence of intraperitoneal and intranasal oxytocin on sleep-wake behaviour and neurophysiology in rats

Raymond

Gururajan

Bowen

2022

Preprint

View full text Add to dashboard Cite

Introduction: Exogenous administration of the neuropeptide oxytocin exerts diverse effects on various neurobehavioural processes, including sleep and wakefulness. Since oxytocin can enhance attention to social and fear-related environmental cues, it should promote arousal and wakefulness. However, as oxytocin can attenuate stress, reduce activity, and elicit anxiolysis, oxytocin might also prime the brain for rest and promote sleep. At present, little research has comprehensively characterised the neuropsychopharmacology of oxytocin-induced effects on sleep-wake behaviour and no reconciliation of these two competing hypotheses has been proposed. Methods: This study explored the effects of oxytocin on sleep-wake outcomes using radiotelemetry-based polysomnography in adult male and female Wistar rats. Oxytocin was administered via intraperitoneal (i.p.; 0.1, 0.3 and 1 mg·kg-1) and intranasal (i.n.; 0.06, 1, 3 mg·kg-1) routes. Caffeine (i.p. and i.n.; 10 mg·kg-1) was administered as a wake-promoting positive control. To ascertain mechanism of action, pre-treatment experiments with the oxytocin receptor (OXTR) antagonist L-368,899 (i.p.; 5 mg·kg-1) followed by oxytocin (i.p.; 1 mg·kg-1) were also conducted. Results: In both male and female rats, i.p. oxytocin promoted quiet wakefulness at the cost of suppressing active wakefulness, NREM and REM sleep. Several i.p. oxytocin-induced sleep-wake effects were mediated by OXTR binding. In contrast, i.n. oxytocin did not alter most sleep-wake outcomes at any dose tested. Both i.p. and i.n. caffeine demonstrated wake-promoting effects. Conclusions: These findings help reconcile competing hypotheses of oxytocin-induced effects on sleep-wake behaviour: i.p. oxytocin promotes quiet wakefulness, a state of restful environmental awareness compatible with both oxytocin-induced anxiolytic effects and its enhancement of processing complex stimuli.

show abstract

“…At the same time, studies have found that 5‐HT in the central system also plays a vital role in regulating the body's sleep–wake cycle 19 . Several studies have suggested that 5‐HT neurons in the dorsal raphe nucleus (DRN) function predominantly to promote wakefulness and inhibit rapid eye movement (REM) 20 . On the other hand, sleep deprivation can induce changes in 5‐HT actions and 5‐HT 1A receptor expression in the rat hippocampus 21 .…”

Section: Introductionmentioning

confidence: 99%

Variation in the sexual behavior and blood count parameters induced by sleep deprivation in male rats

Zhang

et al. 2022

Andrology

View full text Add to dashboard Cite

Background: Sleep is a fundamental biological requirement, and lack of sleep has increasingly been recognized to cause metabolic consequences and adversely affect immune function. Recent articles have pointed to how sleep and sexual functions may be interlinked, involving inflammation, vascular alterations, tissue damage, and endothelial dysfunction. Objectives:We examined the effect of paradoxical sleep deprivation on sexual behavior and hemogram parameters in male rats. In addition, we also explored whether 7 days of recovery sleep is sufficient to offset these detriments. Materials and methods: Male rats were given sexual experience through training. At the fifth test, the sexually vigorous males were randomly separated into three experimental groups: paradoxical sleep deprivation (rats submitted to 96 h of paradoxical sleep deprivation, n = 6), recovery sleep (recovery sleep 7 days after paradoxical sleep deprivation, n = 6), and control (n = 10). We evaluated the sexual behaviors of three groups. Blood samples were collected to analyze hemogram parameters.Results: In this study, we recognized that repeated copulatory tests can lead to changes in sexual behavior over time. We found that 96 h of acute sleep deprivation impaired the sexual behavior of male rats. Our results demonstrated that 96 h of paradoxical sleep deprivation also increased levels of white blood cell subpopulations, in particular neutrophils. Recovery sleep after sleep deprivation has a certain reversal effect on white blood cell subgroups and impairment of sexual behavior, with some signs that not all levels were back to baseline even after 7 days of recovery. Conclusion:In general, we found that 96 h of paradoxical sleep deprivation impaired the sexual behavior of male rats. Our results demonstrated that paradoxical sleep deprivation can cause systemic inflammation by affecting white blood cell subpopulations, in particular neutrophils. Seven days of recovery sleep after sleep deprivation has a certain reversal effect to these impairments.

show abstract

Optogenetic activation of DRN 5-HT neurons induced active wakefulness, not quiet wakefulness

Cited by 17 publications

References 54 publications

Functional Interaction Between GABAergic Neurons in the Ventral Tegmental Area and Serotonergic Neurons in the Dorsal Raphe Nucleus

Functional Interaction Between GABAergic Neurons in the Ventral Tegmental Area and Serotonergic Neurons in the Dorsal Raphe Nucleus

Quiet wakefulness: The influence of intraperitoneal and intranasal oxytocin on sleep-wake behaviour and neurophysiology in rats

Variation in the sexual behavior and blood count parameters induced by sleep deprivation in male rats

Contact Info

Product

Resources

About