73 results on '"Cherasse Y"'
Search Results
2. Sleep is regulated by prostaglandin D2 selectively produced in the meninges by lipocalin-type prostaglandin D synthase: P16-69
- Author
-
Cherasse, Y., Oishi, Y., Lazarus, M., Huang, Z.-L., Hayaishi, O., and Urade, Y.
- Published
- 2012
3. Activation of adenosine A2A receptors in the olfactory tubercle promotes sleep in rodents
- Author
-
Wang, Y.-Q., primary, Li, R., additional, Liu, W.-Y., additional, Zhang, M.-Q., additional, Li, L., additional, Cherasse, Y., additional, Schiffmann, S.N., additional, de Kerchove d'Exaerde, A., additional, Lazarus, M., additional, Qu, W.-M., additional, and Huang, Z.-L., additional
- Published
- 2019
- Full Text
- View/download PDF
4. La cataplexie, perte de tonus musculaire pendant l’éveil, emprunte t’elle le même réseau neuronal que l’atonie musculaire du sommeil paradoxal ?
- Author
-
Roman, A., primary, Villalba, M., additional, Morel, A.L., additional, Cherasse, Y., additional, Lazarus, M., additional, Luppi, P.H., additional, Libourel, P.A., additional, and Peyron, C., additional
- Published
- 2018
- Full Text
- View/download PDF
5. The relationship between sleep, cannabinoids and seizures
- Author
-
Malyshevskaya, O., primary, Aritake, K., additional, Kaushik, M.K., additional, Uchiyama, N., additional, Cherasse, Y., additional, Kikura-Hanajiri, R., additional, and Urade, Y., additional
- Published
- 2017
- Full Text
- View/download PDF
6. Zinc improves sleep quality in human and promotes non-rapid eye movement sleep in mice
- Author
-
Cherasse, Y., primary, Saito, H., additional, and Urade, Y., additional
- Published
- 2017
- Full Text
- View/download PDF
7. Allosteric modulation of adenosine A2A receptors in mice induces slow-wave sleep without cardiovascular effects
- Author
-
Korkutata, M., primary, Saitoh, T., additional, Feng, D., additional, Murakoshi, N., additional, Sugiyama, F., additional, Cherasse, Y., additional, Nagase, H., additional, and Lazarus, M., additional
- Published
- 2017
- Full Text
- View/download PDF
8. Dopamine D1 receptor subtype mediates acute stress-induced dendritic growth in excitatory neurons of the medial prefrontal cortex and contributes to suppression of stress susceptibility in mice
- Author
-
Shinohara, R, primary, Taniguchi, M, additional, Ehrlich, A T, additional, Yokogawa, K, additional, Deguchi, Y, additional, Cherasse, Y, additional, Lazarus, M, additional, Urade, Y, additional, Ogawa, A, additional, Kitaoka, S, additional, Sawa, A, additional, Narumiya, S, additional, and Furuyashiki, T, additional
- Published
- 2017
- Full Text
- View/download PDF
9. Zinc promotes non-rapid eye movement sleep in mice
- Author
-
Cherasse, Y., primary, Saitou, H., additional, and Urade, Y., additional
- Published
- 2015
- Full Text
- View/download PDF
10. Implication of the striatopallidal pathway in Parkinson's disease (PD) related sleep disorder
- Author
-
Cherasse, Y., primary, Zhang, B., additional, Urade, Y., additional, and Lazarus, M., additional
- Published
- 2015
- Full Text
- View/download PDF
11. Amino acid deprivation regulates the stress-inducible gene p8 via the GCN2/ATF4 pathway
- Author
-
Averous, J., primary, Lambert-Langlais, S., additional, Cherasse, Y., additional, Carraro, V., additional, Parry, L., additional, B’chir, W., additional, Jousse, C., additional, Maurin, A.C., additional, Bruhat, A., additional, and Fafournoux, P., additional
- Published
- 2011
- Full Text
- View/download PDF
12. Arousal Effect of Caffeine Depends on Adenosine A2A Receptors in the Shell of the Nucleus Accumbens
- Author
-
Lazarus, M., primary, Shen, H.-Y., additional, Cherasse, Y., additional, Qu, W.-M., additional, Huang, Z.-L., additional, Bass, C. E., additional, Winsky-Sommerer, R., additional, Semba, K., additional, Fredholm, B. B., additional, Boison, D., additional, Hayaishi, O., additional, Urade, Y., additional, and Chen, J.-F., additional
- Published
- 2011
- Full Text
- View/download PDF
13. ATF2 is required for amino acid-regulated transcription by orchestrating specific histone acetylation
- Author
-
Bruhat, A., primary, Cherasse, Y., additional, Maurin, A.-C., additional, Breitwieser, W., additional, Parry, L., additional, Deval, C., additional, Jones, N., additional, Jousse, C., additional, and Fafournoux, P., additional
- Published
- 2007
- Full Text
- View/download PDF
14. Supramammillary nucleus synchronizes with dentate gyrus to regulate spatial memory retrieval through glutamate release
- Author
-
Yadong Li, Hechen Bao, Yanjia Luo, Cherasse Yoan, Heather Anne Sullivan, Luis Quintanilla, Ian Wickersham, Michael Lazarus, Yen-Yu Ian Shih, and Juan Song
- Subjects
SuM-DG correlation ,memory encoding ,memory retrieval ,calcium imaging ,fiber photometry ,SuM glutamate transmission ,Medicine ,Science ,Biology (General) ,QH301-705.5 - Abstract
The supramammillary nucleus (SuM) provides substantial innervation to the dentate gyrus (DG). It remains unknown how the SuM and DG coordinate their activities at the circuit level to regulate spatial memory. Additionally, SuM co-releases GABA and glutamate to the DG, but the relative role of GABA versus glutamate in regulating spatial memory remains unknown. Here we report that SuM-DG Ca2+ activities are highly correlated during spatial memory retrieval as compared to the moderate correlation during memory encoding when mice are performing a location discrimination task. Supporting this evidence, we demonstrate that the activity of SuM neurons or SuM-DG projections is required for spatial memory retrieval. Furthermore, we show that SuM glutamate transmission is necessary for both spatial memory retrieval and highly-correlated SuM-DG activities during spatial memory retrieval. Our studies identify a long-range SuM-DG circuit linking two highly correlated subcortical regions to regulate spatial memory retrieval through SuM glutamate release.
- Published
- 2020
- Full Text
- View/download PDF
15. GCN2 regulates feeding behavior to maintain amino acid homeostasis in omnivores | La kinase GCN2 régule le comportement alimentaire des omnivores afin de maintenir l'homéostasie des acides aminés
- Author
-
Maurin, A. -C, Jousse, C., Balage, M., Averous, J., Parry, L., Bruhat, A., Cherasse, Y., Zeng, H., Zhang, Y., Heather P Harding, Ron, D., and Fafournoux, P.
16. Optochemical control of slow-wave sleep in the nucleus accumbens of male mice by a photoactivatable allosteric modulator of adenosine A 2A receptors.
- Author
-
Roy K, Zhou X, Otani R, Yuan PC, Ioka S, Vogt KE, Kondo T, Farag NHT, Ijiri H, Wu Z, Chitose Y, Amezawa M, Uygun DS, Cherasse Y, Nagase H, Li Y, Yanagisawa M, Abe M, Basheer R, Wang YQ, Saitoh T, and Lazarus M
- Subjects
- Animals, Male, Mice, Allosteric Regulation, Astrocytes metabolism, Astrocytes drug effects, Light, Neurons metabolism, Neurons drug effects, Mice, Inbred C57BL, Humans, Adenosine A2 Receptor Agonists pharmacology, Nucleus Accumbens metabolism, Nucleus Accumbens drug effects, Nucleus Accumbens physiology, Receptor, Adenosine A2A metabolism, Receptor, Adenosine A2A genetics, Adenosine metabolism, Adenosine pharmacology, Sleep, Slow-Wave physiology, Sleep, Slow-Wave drug effects
- Abstract
Optochemistry, an emerging pharmacologic approach in which light is used to selectively activate or deactivate molecules, has the potential to alleviate symptoms, cure diseases, and improve quality of life while preventing uncontrolled drug effects. The development of in-vivo applications for optochemistry to render brain cells photoresponsive without relying on genetic engineering has been progressing slowly. The nucleus accumbens (NAc) is a region for the regulation of slow-wave sleep (SWS) through the integration of motivational stimuli. Adenosine emerges as a promising candidate molecule for activating indirect pathway neurons of the NAc expressing adenosine A
2A receptors (A2A Rs) to induce SWS. Here, we developed a brain-permeable positive allosteric modulator of A2A Rs (A2A R PAM) that can be rapidly photoactivated with visible light (λ > 400 nm) and used it optoallosterically to induce SWS in the NAc of freely behaving male mice by increasing the activity of extracellular adenosine derived from astrocytic and neuronal activity., (© 2024. The Author(s).)- Published
- 2024
- Full Text
- View/download PDF
17. A novel GABAergic population in the medial vestibular nucleus maintains wakefulness and gates rapid eye movement sleep.
- Author
-
Nakatsuka D, Kanda T, Sato M, Ishikawa Y, Cherasse Y, and Yanagisawa M
- Abstract
Body rocking can either induce sleep or arousal. That is, the vestibular sense influences sleep-wake states. Neuronal interactions between sleep-wake systems and vestibular systems, however, remain unclear. In this study, we found that GABAergic neurons in the lateral part of the medial vestibular nucleus (LMVN), a primary vestibular afferent projection site, control sleep-wake states. Specific inhibition of LMVN GABAergic neurons revealed that the firing of LMVN GABAergic neurons underlies stable wakefulness and smooth transitions from non-rapid-eye-movement (NREM) sleep to rapid eye movement (REM) sleep and that LMVN GABAergic neurons do not affect body balance control in freely moving conditions. Selective axonal tracing of LMVN GABAergic neurons indicated that LMVN GABAergic neurons send axons not only to areas involved in vestibular and oculomotor functions but also to areas regulating sleep-wake states. Our findings suggest that LMVN GABAergic neurons stabilize wakefulness and gate the entry into REM sleep through the use of vestibular information., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
18. Association between idiopathic hypersomnia and a genetic variant in the PER3 gene.
- Author
-
Cherasse Y, Taira Y, Rassu AL, Barateau L, Evangelista E, Muratani M, Funato H, Yanagisawa M, and Dauvilliers Y
- Abstract
We aim to identify genetic markers associated with idiopathic hypersomnia, a disabling orphan central nervous system disorder of hypersomnolence that is still poorly understood. In our study, DNA was extracted from 79 unrelated patients diagnosed with idiopathic hypersomnia with long sleep time at the National Reference Center for Narcolepsy-France according to very stringent diagnostic criteria. Whole exome sequencing on the first 30 patients with idiopathic hypersomnia (25 females and 5 males) allowed the single nucleotide variants to be compared with a control population of 574 healthy subjects from the French Exome project database. We focused on the identification of genetic variants among 182 genes related to the regulation of sleep and circadian rhythm. Candidate variants obtained by exome sequencing analysis were then validated in a second sample of 49 patients with idiopathic hypersomnia (37 females and 12 males). Our study characterised seven variants from six genes significantly associated with idiopathic hypersomnia compared with controls. A targeted sequencing analysis of these seven variants on 49 other patients with idiopathic hypersomnia confirmed the relative over-representation of the A➔C variant of rs2859390, located in a potential splicing-site of PER3 gene. Our findings support a genetic predisposition and identify pathways involved in the pathogeny of idiopathic hypersomnia. A variant of the PER3 gene may predispose to idiopathic hypersomnia with long sleep time., (© 2024 European Sleep Research Society.)
- Published
- 2024
- Full Text
- View/download PDF
19. Positive allosteric adenosine A 2A receptor modulation suppresses insomnia associated with mania- and schizophrenia-like behaviors in mice.
- Author
-
Lin Y, Roy K, Ioka S, Otani R, Amezawa M, Ishikawa Y, Cherasse Y, Kaushik MK, Klewe-Nebenius D, Zhou L, Yanagisawa M, Oishi Y, Saitoh T, and Lazarus M
- Abstract
Background: Insomnia is associated with psychiatric illnesses such as bipolar disorder or schizophrenia. Treating insomnia improves psychotic symptoms severity, quality of life, and functional outcomes. Patients with psychiatric disorders are often dissatisfied with the available therapeutic options for their insomnia. In contrast, positive allosteric modulation of adenosine A
2A receptors (A2A Rs) leads to slow-wave sleep without cardiovascular side effects in contrast to A2A R agonists. Methods: We investigated the hypnotic effects of A2A R positive allosteric modulators (PAMs) in mice with mania-like behavior produced by ablating GABAergic neurons in the ventral medial midbrain/pons area and in a mouse model of schizophrenia by knocking out of microtubule-associated protein 6. We also compared the properties of sleep induced by A2A R PAMs in mice with mania-like behavior with those induced by DORA-22, a dual orexin receptor antagonist that improves sleep in pre-clinical models, and the benzodiazepine diazepam. Results: A2A R PAMs suppress insomnia associated with mania- or schizophrenia-like behaviors in mice. A2A R PAM-mediated suppression of insomnia in mice with mania-like behavior was similar to that mediated by DORA-22, and, unlike diazepam, did not result in abnormal sleep. Conclusion: A2A R allosteric modulation may represent a new therapeutic avenue for sleep disruption associated with bipolar disorder or psychosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lin, Roy, Ioka, Otani, Amezawa, Ishikawa, Cherasse, Kaushik, Klewe-Nebenius, Zhou, Yanagisawa, Oishi, Saitoh and Lazarus.)- Published
- 2023
- Full Text
- View/download PDF
20. Motivational and Valence-Related Modulation of Sleep/Wake Behavior are Mediated by Midbrain Dopamine and Uncoupled from the Homeostatic and Circadian Processes.
- Author
-
Fifel K, El Farissi A, Cherasse Y, and Yanagisawa M
- Subjects
- Circadian Rhythm physiology, Mesencephalon physiology, Sleep physiology, Dopamine, Motivation
- Abstract
Motivation and its hedonic valence are powerful modulators of sleep/wake behavior, yet its underlying mechanism is still poorly understood. Given the well-established role of midbrain dopamine (mDA) neurons in encoding motivation and emotional valence, here, neuronal mechanisms mediating sleep/wake regulation are systematically investigated by DA neurotransmission. It is discovered that mDA mediates the strong modulation of sleep/wake states by motivational valence. Surprisingly, this modulation can be uncoupled from the classically employed measures of circadian and homeostatic processes of sleep regulation. These results establish the experimental foundation for an additional new factor of sleep regulation. Furthermore, an electroencephalographic marker during wakefulness at the theta range is identified that can be used to reliably track valence-related modulation of sleep. Taken together, this study identifies mDA signaling as an important neural substrate mediating sleep modulation by motivational valence., (© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.)
- Published
- 2022
- Full Text
- View/download PDF
21. Lateral habenula glutamatergic neurons projecting to the dorsal raphe nucleus promote aggressive arousal in mice.
- Author
-
Takahashi A, Durand-de Cuttoli R, Flanigan ME, Hasegawa E, Tsunematsu T, Aleyasin H, Cherasse Y, Miya K, Okada T, Keino-Masu K, Mitsui K, Li L, Patel V, Blitzer RD, Lazarus M, Tanaka KF, Yamanaka A, Sakurai T, Ogawa S, and Russo SJ
- Subjects
- Aggression physiology, Animals, Arousal, Male, Mice, Neural Pathways physiology, Neurons metabolism, Dorsal Raphe Nucleus physiology, Habenula physiology
- Abstract
The dorsal raphe nucleus (DRN) is known to control aggressive behavior in mice. Here, we found that glutamatergic projections from the lateral habenula (LHb) to the DRN were activated in male mice that experienced pre-exposure to a rival male mouse ("social instigation") resulting in heightened intermale aggression. Both chemogenetic and optogenetic suppression of the LHb-DRN projection blocked heightened aggression after social instigation in male mice. In contrast, inhibition of this pathway did not affect basal levels of aggressive behavior, suggesting that the activity of the LHb-DRN projection is not necessary for the expression of species-typical aggressive behavior, but required for the increase of aggressive behavior resulting from social instigation. Anatomical analysis showed that LHb neurons synapse on non-serotonergic DRN neurons that project to the ventral tegmental area (VTA), and optogenetic activation of the DRN-VTA projection increased aggressive behaviors. Our results demonstrate that the LHb glutamatergic inputs to the DRN promote aggressive arousal induced by social instigation, which contributes to aggressive behavior by activating VTA-projecting non-serotonergic DRN neurons as one of its potential targets., (© 2022. The Author(s).)
- Published
- 2022
- Full Text
- View/download PDF
22. Hypothalamic modulation of adult hippocampal neurogenesis in mice confers activity-dependent regulation of memory and anxiety-like behavior.
- Author
-
Li YD, Luo YJ, Chen ZK, Quintanilla L, Cherasse Y, Zhang L, Lazarus M, Huang ZL, and Song J
- Subjects
- Animals, Anxiety, Hypothalamus, Memory physiology, Mice, Mice, Inbred C57BL, Hippocampus physiology, Neurogenesis physiology
- Abstract
Adult hippocampal neurogenesis plays a critical role in memory and emotion processing, and this process is dynamically regulated by neural circuit activity. However, it remains unknown whether manipulation of neural circuit activity can achieve sufficient neurogenic effects to modulate behavior. Here we report that chronic patterned optogenetic stimulation of supramammillary nucleus (SuM) neurons in the mouse hypothalamus robustly promotes neurogenesis at multiple stages, leading to increased production of neural stem cells and behaviorally relevant adult-born neurons (ABNs) with enhanced maturity. Functionally, selective manipulation of the activity of these SuM-promoted ABNs modulates memory retrieval and anxiety-like behaviors. Furthermore, we show that SuM neurons are highly responsive to environmental novelty (EN) and are required for EN-induced enhancement of neurogenesis. Moreover, SuM is required for ABN activity-dependent behavioral modulation under a novel environment. Our study identifies a key hypothalamic circuit that couples novelty signals to the production and maturation of ABNs, and highlights the activity-dependent contribution of circuit-modified ABNs in behavioral regulation., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)
- Published
- 2022
- Full Text
- View/download PDF
23. Rapid eye movement sleep is initiated by basolateral amygdala dopamine signaling in mice.
- Author
-
Hasegawa E, Miyasaka A, Sakurai K, Cherasse Y, Li Y, and Sakurai T
- Subjects
- Animals, Cataplexy physiopathology, Male, Mice, Mice, Inbred C57BL, Neurons metabolism, Receptors, Dopamine D2 metabolism, Signal Transduction, Sleep physiology, Wakefulness, Basolateral Nuclear Complex metabolism, Dopamine metabolism, Sleep, REM physiology
- Abstract
The sleep cycle is characterized by alternating non-rapid eye movement (NREM) and rapid eye movement (REM) sleeps. The mechanisms by which this cycle is generated are incompletely understood. We found that a transient increase of dopamine (DA) in the basolateral amygdala (BLA) during NREM sleep terminates NREM sleep and initiates REM sleep. DA acts on dopamine receptor D2 (Drd2)-expressing neurons in the BLA to induce the NREM-to-REM transition. This mechanism also plays a role in cataplectic attacks-a pathological intrusion of REM sleep into wakefulness-in narcoleptics. These results show a critical role of DA signaling in the BLA in initiating REM sleep and provide a neuronal basis for sleep cycle generation.
- Published
- 2022
- Full Text
- View/download PDF
24. Open-Source Software for Real-time Calcium Imaging and Synchronized Neuron Firing Detection.
- Author
-
Taniguchi M, Tezuka T, Vergara P, Srinivasan S, Hosokawa T, Cherasse Y, Naoi T, Sakurai T, and Sakaguchi M
- Subjects
- Animals, Brain diagnostic imaging, Optogenetics, Software, Calcium, Neurons
- Abstract
We developed Carignan, a real-time calcium imaging software that can automatically detect activity patterns of neurons. Carignan can activate an external device when synchronized neural activity is detected in calcium imaging obtained by a one-photon (1p) miniscope. Combined with optogenetics, our software enables closed-loop experiments for investigating functions of specific types of neurons in the brain. In addition to making existing pattern detection algorithms run in real-time seamlessly, we developed a new classification module that distinguishes neurons from false-positives using deep learning. We used a combination of convolutional and recurrent neural networks to incorporate both spatial and temporal features in activity patterns. Our method performed better than existing neuron detection methods for false-positive neuron detection in terms of the F1 score. Using Carignan, experimenters can activate or suppress a group of neurons when specific neural activity is observed. Because the system uses a 1p miniscope, it can be used on the brain of a freely-moving animal, making it applicable to a wide range of experimental paradigms.
- Published
- 2021
- Full Text
- View/download PDF
25. Induction of narcolepsy-like symptoms by orexin receptor antagonists in mice.
- Author
-
Kaushik MK, Aritake K, Cherasse Y, Imanishi A, Kanbayashi T, Urade Y, and Yanagisawa M
- Subjects
- Animals, Dogs, Humans, Mice, Mice, Knockout, Orexin Receptor Antagonists pharmacology, Orexin Receptor Antagonists therapeutic use, Orexin Receptors, Orexins therapeutic use, Rats, Cataplexy drug therapy, Narcolepsy drug therapy
- Abstract
Orexins/hypocretins are hypothalamic neuropeptides that promote and stabilize wakefulness by binding to the orexin receptor type-1 (OX1R) and type-2 (OX2R). Disruption of orexinergic signaling results in the sleep disorder narcolepsy in mice, rats, dogs, and humans. The orexin receptor antagonist suvorexant promotes sleep by blocking both OX1R and OX2R. Whereas suvorexant has been clinically approved for the treatment of insomnia because it is well tolerated in experimental animals as well as in human patients, a logical question remains as to why orexin receptor antagonists do not induce overt narcolepsy-like symptoms. Here we show that acute and chronic suvorexant promotes both rapid eye movement (REM) and non-rapid eye movement (NREM) sleep without inducing cataplexy in mice. Interestingly, chronic suvorexant increases OX2R mRNA and decreases orexin mRNA and peptide levels, which remain low long after termination of suvorexant administration. When mice are chronically treated with suvorexant and then re-challenged with the antagonist after a 1-week washout, however, cataplexy and sleep-onset REM (SOREM) are observed, which are exacerbated by chocolate administration. Heterozygous orexin knockout mice, with lower brain orexin levels, show cataplexy and SOREM after acute suvorexant administration. Furthermore, we find that acute suvorexant can induce cataplexy and SOREM in wild-type mice when co-administered with chocolate under stress-free (temporally anesthetized) conditions. Taken together, these results suggest that suvorexant can inhibit orexin synthesis resulting in susceptibility to narcolepsy-like symptoms in mice under certain conditions., (© Sleep Research Society 2021. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
- Published
- 2021
- Full Text
- View/download PDF
26. Chronic Stress Induces Sex-Specific Functional and Morphological Alterations in Corticoaccumbal and Corticotegmental Pathways.
- Author
-
Bittar TP, Pelaez MC, Hernandez Silva JC, Quessy F, Lavigne AA, Morency D, Blanchette LJ, Arsenault E, Cherasse Y, Seigneur J, Timofeev I, Sephton CF, Proulx CD, and Labonté B
- Subjects
- Animals, Female, Male, Mice, Mice, Inbred C57BL, Neurons, Prefrontal Cortex, Nucleus Accumbens, Ventral Tegmental Area
- Abstract
Background: The medial prefrontal cortex (mPFC) is part of a complex circuit controlling stress responses by sending projections to different limbic structures including the nucleus accumbens (NAc) and ventral tegmental area (VTA). However, the impact of chronic stress on NAc- and VTA-projecting mPFC neurons is still unknown, and the distinct contribution of these pathways to stress responses in males and females is unclear., Methods: Behavioral stress responses were induced by 21 days of chronic variable stress in male and female C57BL/6NCrl mice. An intersectional viral approach was used to label both pathways and assess the functional, morphological, and transcriptional adaptations in NAc- and VTA-projecting mPFC neurons in stressed males and females. Using chemogenetic approaches, we modified neuronal activity of NAc-projecting mPFC neurons to decipher their contribution to stress phenotypes., Results: Chronic variable stress induced depressive-like behaviors in males and females. NAc- and VTA-projecting mPFC neurons exhibited sex-specific functional, morphological, and transcriptional alterations. The functional changes were more severe in females in NAc-projecting mPFC neurons, while males exhibited more drastic reductions in dendritic complexity in VTA-projecting mPFC neurons after chronic variable stress. Finally, chemogenetic overactivation of the corticoaccumbal pathway triggered anxiety and behavioral despair in both sexes, while its inhibition rescued the phenotype only in females., Conclusions: Our results suggest that stress responses in males and females result from pathway-specific changes in the activity of transcriptional programs controlling the morphological and synaptic properties of corticoaccumbal and corticotegmental pathways in a sex-specific fashion., (Copyright © 2021 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
27. Ventral pallidal GABAergic neurons control wakefulness associated with motivation through the ventral tegmental pathway.
- Author
-
Li YD, Luo YJ, Xu W, Ge J, Cherasse Y, Wang YQ, Lazarus M, Qu WM, and Huang ZL
- Subjects
- Animals, GABAergic Neurons, Mice, Motivation, Ventral Tegmental Area, Basal Forebrain, Wakefulness
- Abstract
The ventral pallidum (VP) regulates motivation, drug addiction, and several behaviors that rely on heightened arousal. However, the role and underlying neural circuits of the VP in the control of wakefulness remain poorly understood. In the present study, we sought to elucidate the specific role of VP GABAergic neurons in controlling sleep-wake behaviors in mice. Fiber photometry revealed that the population activity of VP GABAergic neurons was increased during physiological transitions from non-rapid eye movement (non-REM, NREM) sleep to either wakefulness or REM sleep. Moreover, chemogenetic and optogenetic manipulations were leveraged to investigate a potential causal role of VP GABAergic neurons in initiating and/or maintaining arousal. In vivo optogenetic stimulation of VP GABAergic neurons innervating the ventral tegmental area (VTA) strongly promoted arousal via disinhibition of VTA dopaminergic neurons. Functional in vitro mapping revealed that VP GABAergic neurons, in principle, inhibited VTA GABAergic neurons but also inhibited VTA dopaminergic neurons. In addition, optogenetic stimulation of terminals of VP GABAergic neurons revealed that they promoted arousal by innervating the lateral hypothalamus, but not the mediodorsal thalamus or lateral habenula. The increased wakefulness chemogenetically evoked by VP GABAergic neuronal activation was completely abolished by pretreatment with dopaminergic D
1 and D2 /D3 receptor antagonists. Furthermore, activation of VP GABAergic neurons increased exploration time in both the open-field and light-dark box tests but did not modulate depression-like behaviors or food intake. Finally, chemogenetic inhibition of VP GABAergic neurons decreased arousal. Taken together, our findings indicate that VP GABAergic neurons are essential for arousal related to motivation., (© 2020. The Author(s).)- Published
- 2021
- Full Text
- View/download PDF
28. Medial Parabrachial Nucleus Is Essential in Controlling Wakefulness in Rats.
- Author
-
Xu Q, Wang DR, Dong H, Chen L, Lu J, Lazarus M, Cherasse Y, Chen GH, Qu WM, and Huang ZL
- Abstract
Activation of the parabrachial nucleus (PB) in the brainstem induced wakefulness in rats, suggesting which is an important nucleus that controls arousal. However, the sub-regions of PB in regulating sleep-wake cycle is still unclear. Here, we employ chemogenetics and optogenetics strategies and find that activation of the medial part of PB (MPB), but not the lateral part, induces continuous wakefulness for 10 h without sleep rebound in neither sleep amount nor the power spectra. Optogenetic activation of glutamatergic MPB neurons in sleeping rats immediately wake rats mediated by the basal forebrain (BF) and lateral hypothalamus (LH), but not the ventral medial thalamus. Most importantly, chemogenetic inhibition of PB neurons decreases wakefulness for 10 h. Conclusively, these findings indicate that the glutamatergic MPB neurons are essential in controlling wakefulness, and that MPB-BF and MPB-LH pathways are the major neuronal circuits., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Xu, Wang, Dong, Chen, Lu, Lazarus, Cherasse, Chen, Qu and Huang.)
- Published
- 2021
- Full Text
- View/download PDF
29. Ablation of Ventral Midbrain/Pons GABA Neurons Induces Mania-like Behaviors with Altered Sleep Homeostasis and Dopamine D 2 R-mediated Sleep Reduction.
- Author
-
Honda T, Takata Y, Cherasse Y, Mizuno S, Sugiyama F, Takahashi S, Funato H, Yanagisawa M, Lazarus M, and Oishi Y
- Abstract
Individuals with the neuropsychiatric disorder mania exhibit hyperactivity, elevated mood, and a decreased need for sleep. The brain areas and neuronal populations involved in mania-like behaviors, however, have not been elucidated. In this study, we found that ablating the ventral medial midbrain/pons (VMP) GABAergic neurons induced mania-like behaviors in mice, including hyperactivity, anti-depressive behaviors, reduced anxiety, increased risk-taking behaviors, distractibility, and an extremely shortened sleep time. Strikingly, these mice also showed no rebound sleep after sleep deprivation, suggesting abnormal sleep homeostatic regulation. Dopamine D
2 receptor deficiency largely abolished the sleep reduction induced by ablating the VMP GABAergic neurons without affecting the hyperactivity and anti-depressive behaviors. Our data demonstrate that VMP GABAergic neurons are involved in the expression of mania-like behaviors, which can be segregated to the short-sleep and other phenotypes on the basis of the dopamine D2 receptors., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)- Published
- 2020
- Full Text
- View/download PDF
30. Activation of adenosine A 2A receptors in the olfactory tubercle promotes sleep in rodents.
- Author
-
Li R, Wang YQ, Liu WY, Zhang MQ, Li L, Cherasse Y, Schiffmann SN, de Kerchove d'Exaerde A, Lazarus M, Qu WM, and Huang ZL
- Subjects
- Adenosine analogs & derivatives, Adenosine pharmacology, Animals, Electroencephalography methods, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Olfactory Tubercle drug effects, Phenethylamines pharmacology, Rats, Rats, Sprague-Dawley, Receptor, Adenosine A2A genetics, Rodentia, Sleep drug effects, Adenosine A2 Receptor Agonists pharmacology, Olfactory Tubercle metabolism, Receptor, Adenosine A2A metabolism, Sleep physiology
- Abstract
The olfactory tubercle (OT), an important nucleus in processing sensory information, has been reported to change cortical activity under odor. However, little is known about the physiological role and mechanism of the OT in sleep-wake regulation. The OT expresses abundant adenosine A
2A receptors (A2A Rs), which are important in sleep regulation. Therefore, we hypothesized that the OT regulates sleep via A2A Rs. This study examined sleep-wake profiles through electroencephalography and electromyography recordings with pharmacological and chemogenetic manipulations in freely moving rodents. Compared with their controls, activation of OT A2A Rs pharmacologically and OT A2A R neurons via chemogenetics increased non-rapid eye movement sleep for 5 and 3 h, respectively, while blockade of A2A Rs decreased non-rapid eye movement sleep. Tracing and electrophysiological studies showed OT A2A R neurons projected to the ventral pallidum and lateral hypothalamus, forming inhibitory innervations. Together, these findings indicate that A2A Rs in the OT play an important role in sleep regulation., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2019. Published by Elsevier Ltd.)- Published
- 2020
- Full Text
- View/download PDF
31. Corrigendum to "Enhancing endogenous adenosine A 2A receptor signaling induces slow-wave sleep without affecting body temperature and cardiovascular function" [Neuropharmacology 144 (2019) 122-132].
- Author
-
Korkutata M, Saitoh T, Cherasse Y, Ioka S, Duo F, Qin R, Murakoshi N, Fujii S, Zhou X, Sugiyama F, Chen JF, Kumagai H, Nagase H, and Lazarus M
- Published
- 2019
- Full Text
- View/download PDF
32. Extracellular adenosine and slow-wave sleep are increased after ablation of nucleus accumbens core astrocytes and neurons in mice.
- Author
-
Zhou X, Oishi Y, Cherasse Y, Korkutata M, Fujii S, Lee CY, and Lazarus M
- Subjects
- Ablation Techniques methods, Animals, Mice, Mice, Knockout, Mice, Transgenic, Nucleus Accumbens surgery, Receptor, Adenosine A2A metabolism, Adenosine metabolism, Astrocytes metabolism, Extracellular Fluid metabolism, Neurons metabolism, Nucleus Accumbens metabolism, Sleep, Slow-Wave physiology
- Abstract
Sleep and wakefulness are controlled by a wide range of neuronal populations in the mammalian brain. Activation of adenosine A
2A receptor (A2A R)-expressing neurons in the nucleus accumbens (NAc) core promotes slow-wave sleep (SWS). The neuronal mechanism by which activation of NAc A2A R neurons induces SWS, however, is unknown. We hypothesized that the ability of NAc activation to induce sleep is mediated by the classic somnogen adenosine, which can be formed by various processes in all types of cells. Here, to investigate whether astrocytes are involved in the ability of the NAc to regulate SWS, we ablated glial fibrillary acidic protein (GFAP)-positive cells in the NAc core of mice by virus-mediated expression of diphtheria toxin (DT) receptors and intraperitoneal administration of DT. Analysis of electroencephalogram and electromyogram recordings of DT-treated wild-type mice revealed that SWS was remarkably increased at 1 week after DT treatment, whereas sleep-wake behavior was unchanged in DT-treated A2A R knockout mice. Cell ablation was associated with an increased number of GFAP-positive cells and activation of microglia in the NAc. In-vivo microdialysis revealed significantly increased levels of extracellular adenosine in the NAc at 1 week after DT treatment. Our findings suggest that elevated adenosine levels in the NAc core promote SWS by acting on A2A Rs and provide the first evidence that adenosine is an endogenous candidate for activating NAc A2A R neurons that have the ability to induce SWS., (Copyright © 2019 Elsevier Ltd. All rights reserved.)- Published
- 2019
- Full Text
- View/download PDF
33. Enhancing endogenous adenosine A 2A receptor signaling induces slow-wave sleep without affecting body temperature and cardiovascular function.
- Author
-
Korkutata M, Saitoh T, Cherasse Y, Ioka S, Duo F, Qin R, Murakoshi N, Fujii S, Zhou X, Sugiyama F, Chen JF, Kumagai H, Nagase H, and Lazarus M
- Subjects
- Adenosine analogs & derivatives, Adenosine metabolism, Adenosine pharmacology, Adenosine A2 Receptor Agonists chemical synthesis, Allosteric Regulation, Animals, Blood Pressure drug effects, Blood Pressure physiology, Body Temperature drug effects, CHO Cells, Cricetulus, Drug Evaluation, Preclinical, Heart Rate drug effects, Heart Rate physiology, Male, Mice, Inbred C57BL, Mice, Knockout, Phenethylamines pharmacology, Random Allocation, Receptor, Adenosine A2A genetics, Receptor, Adenosine A2A metabolism, Signal Transduction drug effects, Sleep, Slow-Wave physiology, Wakefulness drug effects, Wakefulness physiology, Adenosine A2 Receptor Agonists pharmacology, Hypnotics and Sedatives pharmacology, Sleep, Slow-Wave drug effects
- Abstract
Insomnia is one of the most common sleep problems with an estimated prevalence of 10%-15% in the general population. Although adenosine A
2A receptor (A2A R) agonists strongly induce sleep, their cardiovascular effects preclude their use in treating sleep disorders. Enhancing endogenous A2A R signaling, however, may be an alternative strategy for treating insomnia, because adenosine levels in the brain accumulate during wakefulness. In the present study, we found that 3,4-difluoro-2-((2-fluoro-4-iodophenyl)amino)benzoic acid, denoted A2A R positive allosteric modulator (PAM)-1, enhanced adenosine signaling at the A2A R and induced slow wave sleep (SWS) without affecting body temperature in wild-type male mice after intraperitoneal administration, whereas the SWS-inducing effect of this benzoic acid derivative was abolished in A2A R KO mice. In contrast to the A2A R agonist CGS 21680, the A2A R PAM-1 did not affect blood pressure or heart rate. These findings indicate that enhancing A2A R signaling promotes SWS without cardiovascular effects. Therefore, small molecules that allosterically modulate A2A Rs could help people with insomnia to fall asleep., (Copyright © 2018 Elsevier Ltd. All rights reserved.)- Published
- 2019
- Full Text
- View/download PDF
34. Sleep and Wakefulness Are Controlled by Ventral Medial Midbrain/Pons GABAergic Neurons in Mice.
- Author
-
Takata Y, Oishi Y, Zhou XZ, Hasegawa E, Takahashi K, Cherasse Y, Sakurai T, and Lazarus M
- Subjects
- Animals, Dopamine Antagonists pharmacology, Electroencephalography methods, GABAergic Neurons drug effects, Male, Mesencephalon drug effects, Mice, Mice, Inbred C57BL, Mice, Transgenic, Pons drug effects, Sleep drug effects, Wakefulness drug effects, GABAergic Neurons physiology, Mesencephalon physiology, Pons physiology, Sleep physiology, Wakefulness physiology
- Abstract
Sleep-wake behavior is controlled by a wide range of neuronal populations in the mammalian brain. Although the ventral midbrain/pons (VMP) area is suggested to participate in sleep-wake regulation, the neuronal mechanisms have remained unclear. Here, we found that nonspecific cell ablation or selective ablation of GABAergic neurons by expressing diphtheria toxin fragment A in the VMP in male mice induced a large increase in wakefulness that lasted at least 4 weeks. In contrast, selective ablation of dopaminergic neurons in the VMP had little effect on wakefulness. Chemogenetic inhibition of VMP GABAergic neurons also markedly increased wakefulness. The wake-promoting effect of the VMP GABAergic neuron ablation or inhibition was attenuated to varying degrees by the administration of dopamine D1 or D2/3 receptor antagonists and abolished by the administration of both antagonists together. In contrast, chemogenetic activation of VMP GABAergic neurons very strongly increased slow-wave sleep and reduced wakefulness. These findings suggest that VMP GABAergic neurons regulate dopaminergic actions in the sleep-wake behavior of mice. SIGNIFICANCE STATEMENT Current understanding of the neuronal mechanisms and populations that regulate sleep-wake behavior is incomplete. Here, we identified a GABAergic ventral midbrain/pons area that is necessary for controlling the daily amount of sleep and wakefulness in mice. We also found that these inhibitory neurons control wakefulness by suppressing dopaminergic systems. Surprisingly, activation of these neurons strongly induced slow-wave sleep while suppressing wakefulness. Our study reveals a new brain mechanism critical for sleep-wake regulation., (Copyright © 2018 the authors 0270-6474/18/3810080-13$15.00/0.)
- Published
- 2018
- Full Text
- View/download PDF
35. A gain-of-function study of amelioration of pentylenetetrazole-induced seizures by endogenous prostaglandin D 2 .
- Author
-
Kaushik MK, Aritake K, Cherasse Y, Sharma R, and Urade Y
- Subjects
- Animals, Humans, Mice, Knockout, Mice, Transgenic, Prostaglandin D2 pharmacology, Seizures physiopathology, Behavior, Animal drug effects, Gain of Function Mutation drug effects, Pentylenetetrazole pharmacology, Prostaglandin D2 analogs & derivatives, Seizures drug therapy
- Abstract
We previously showed that knockout mice of hematopoietic prostaglandin (PG) D synthase (H-PGDS) produce less PGD
2 to exacerbate pentylenetetrazole (PTZ)-induced seizures. Here, we adopted a gain-of-function strategy and used transgenic mice that over-express human H-PGDS enzyme, to elucidate the role of overproduction of endogenous PGD2 in PTZ-induced seizures. H-PGDS-transgenic mice showed the elevated level of a urinary metabolite of PGD2 , tetranor-PGDM, 3.3- and 2.8-fold higher than the wild-type littermates under the basal condition and after the PTZ administration, respectively, without significantly changing the urinary concentration of a PGE2 -metabolite, tetranor-PGE2 . The intensity of PTZ-induced seizures was decreased in H-PGDS-transgenic mice as evident by the increased seizure onset latency, and a decrease in total duration of generalized tonic-clonic seizures and a total number of EEG seizure spikes during the postictal period (84 s, 17 s, and 5.3/min, respectively), as compared to wild-type mice (53 s, 24 s, and 12.6/min, respectively). These results indicate that overproduction of endogenous PGD2 decreased PTZ-induces seizures., (Copyright © 2018 Elsevier B.V. All rights reserved.)- Published
- 2018
- Full Text
- View/download PDF
36. The Leptomeninges Produce Prostaglandin D 2 Involved in Sleep Regulation in Mice.
- Author
-
Cherasse Y, Aritake K, Oishi Y, Kaushik MK, Korkutata M, and Urade Y
- Abstract
Injection of nanomolar amounts of prostaglandin D
2 (PGD2 ) into the rat brain has dose and time-dependent somnogenic effects, and the PGD2 -induced sleep is indistinguishable from physiologic sleep. Sleep-inducing PGD2 is produced in the brain by lipocalin-type PGD2 synthase (LPGDS). Three potential intracranial sources of LPGDS have been identified: oligodendrocytes, choroid plexus, and leptomeninges. We aimed at the identification of the site of synthesis of somnogenic PGD2 and therefore, generated a transgenic mouse line with the LPGDS gene amenable to conditional deletion using Cre recombinase (flox-LPGDS mouse). To identify the cell type responsible for producing somnogenic PGD2 , we engineered animals lacking LPGDS expression specifically in oligodendrocytes (OD-LPGDS KO), choroid plexus (CP-LPGDS KO), or leptomeninges (LM-LPGDS KO). We measured prostaglandins and LPGDS concentrations together with PGD synthase activity in the brain of these mice. While the LPGDS amount and PGD synthase activity were drastically reduced in the OD- and LM-LPGDS KO mice, they were unchanged in the CP-LPGDS KO mice compared with control animals. We then recorded electroencephalograms, electromyograms, and locomotor activity to measure sleep in 10-week-old mice with specific knockdown of LPGDS in each of the three targets. Using selenium tetrachloride, a specific PGDS inhibitor, we demonstrated that sleep is inhibited in OD-LPGDS and CP-LPGDS KO mice, but not in the LM-LPGDS KO mice. We concluded that somnogenic PGD2 is produced primarily by the leptomeninges, and not by oligodendrocytes or choroid plexus.- Published
- 2018
- Full Text
- View/download PDF
37. Nucleus accumbens controls wakefulness by a subpopulation of neurons expressing dopamine D 1 receptors.
- Author
-
Luo YJ, Li YD, Wang L, Yang SR, Yuan XS, Wang J, Cherasse Y, Lazarus M, Chen JF, Qu WM, and Huang ZL
- Subjects
- Animals, Circadian Rhythm physiology, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Patch-Clamp Techniques, Photometry methods, Receptors, Dopamine D1 biosynthesis, Sleep physiology, Dopaminergic Neurons metabolism, Hypothalamic Area, Lateral physiology, Mesencephalon physiology, Nucleus Accumbens metabolism, Receptors, Dopamine D1 metabolism, Wakefulness physiology
- Abstract
Nucleus accumbens (NAc) is involved in behaviors that depend on heightened wakefulness, but its impact on arousal remains unclear. Here, we demonstrate that NAc dopamine D
1 receptor (D1 R)-expressing neurons are essential for behavioral arousal. Using in vivo fiber photometry in mice, we find arousal-dependent increases in population activity of NAc D1 R neurons. Optogenetic activation of NAc D1 R neurons induces immediate transitions from non-rapid eye movement sleep to wakefulness, and chemogenetic stimulation prolongs arousal, with decreased food intake. Patch-clamp, tracing, immunohistochemistry, and electron microscopy reveal that NAc D1 R neurons project to the midbrain and lateral hypothalamus, and might disinhibit midbrain dopamine neurons and lateral hypothalamus orexin neurons. Photoactivation of terminals in the midbrain and lateral hypothalamus is sufficient to induce wakefulness. Silencing of NAc D1 R neurons suppresses arousal, with increased nest-building behaviors. Collectively, our data indicate that NAc D1 R neuron circuits are essential for the induction and maintenance of wakefulness.- Published
- 2018
- Full Text
- View/download PDF
38. The rostromedial tegmental nucleus is essential for non-rapid eye movement sleep.
- Author
-
Yang SR, Hu ZZ, Luo YJ, Zhao YN, Sun HX, Yin D, Wang CY, Yan YD, Wang DR, Yuan XS, Ye CB, Guo W, Qu WM, Cherasse Y, Lazarus M, Ding YQ, and Huang ZL
- Subjects
- Animals, Channelrhodopsins genetics, Channelrhodopsins metabolism, Clozapine analogs & derivatives, Clozapine pharmacology, Dopamine metabolism, Dopaminergic Neurons cytology, Dopaminergic Neurons drug effects, Dopaminergic Neurons physiology, Dorsal Raphe Nucleus anatomy & histology, Dorsal Raphe Nucleus drug effects, Dorsal Raphe Nucleus physiology, Electrodes, Implanted, Electroencephalography, Genes, Reporter, Ibotenic Acid toxicity, Locus Coeruleus anatomy & histology, Locus Coeruleus drug effects, Locus Coeruleus physiology, Luminescent Proteins genetics, Luminescent Proteins metabolism, Male, Mesencephalon anatomy & histology, Mesencephalon drug effects, Mesencephalon physiology, Neural Pathways anatomy & histology, Neural Pathways drug effects, Optogenetics, Pars Compacta anatomy & histology, Pars Compacta drug effects, Pars Compacta physiology, Rats, Rats, Sprague-Dawley, Receptors, Muscarinic metabolism, Sleep Deprivation physiopathology, Stereotaxic Techniques, Ventral Tegmental Area anatomy & histology, Ventral Tegmental Area drug effects, Wakefulness physiology, gamma-Aminobutyric Acid metabolism, Red Fluorescent Protein, Eye Movements physiology, Neural Pathways physiology, Receptors, Muscarinic genetics, Sleep physiology, Ventral Tegmental Area physiology
- Abstract
The rostromedial tegmental nucleus (RMTg), also called the GABAergic tail of the ventral tegmental area, projects to the midbrain dopaminergic system, dorsal raphe nucleus, locus coeruleus, and other regions. Whether the RMTg is involved in sleep-wake regulation is unknown. In the present study, pharmacogenetic activation of rat RMTg neurons promoted non-rapid eye movement (NREM) sleep with increased slow-wave activity (SWA). Conversely, rats after neurotoxic lesions of 8 or 16 days showed decreased NREM sleep with reduced SWA at lights on. The reduced SWA persisted at least 25 days after lesions. Similarly, pharmacological and pharmacogenetic inactivation of rat RMTg neurons decreased NREM sleep. Electrophysiological experiments combined with optogenetics showed a direct inhibitory connection between the terminals of RMTg neurons and midbrain dopaminergic neurons. The bidirectional effects of the RMTg on the sleep-wake cycle were mimicked by the modulation of ventral tegmental area (VTA)/substantia nigra compacta (SNc) dopaminergic neuronal activity using a pharmacogenetic approach. Furthermore, during the 2-hour recovery period following 6-hour sleep deprivation, the amount of NREM sleep in both the lesion and control rats was significantly increased compared with baseline levels; however, only the control rats showed a significant increase in SWA compared with baseline levels. Collectively, our findings reveal an essential role of the RMTg in the promotion of NREM sleep and homeostatic regulation.
- Published
- 2018
- Full Text
- View/download PDF
39. Activation of Parvalbumin Neurons in the Rostro-Dorsal Sector of the Thalamic Reticular Nucleus Promotes Sensitivity to Pain in Mice.
- Author
-
Liu J, Zhang MQ, Wu X, Lazarus M, Cherasse Y, Yuan MY, Huang ZL, and Li RX
- Subjects
- Animals, GABAergic Neurons cytology, GABAergic Neurons metabolism, Male, Mice, Transgenic, Neuroanatomical Tract-Tracing Techniques, Optogenetics, Parvalbumins metabolism, Thalamus cytology, Thalamus metabolism, GABAergic Neurons physiology, Pain physiopathology, Thalamus physiopathology
- Abstract
The calcium-binding protein, parvalbumin (PV), is highly expressed in thalamic reticular nucleus (TRN) GABAergic neurons, which receive input from the cerebral cortex and thalamus and send inhibitory output to the thalamic relay nucleus. Previous studies suggest that the TRN is involved in pain regulation as an important relay nucleus of the ascending pain pathway. However, little is known about its functional role in pain regulation and interconnectivity. In our study, the role of rostro-dorsal sector of TRN (TRNrd) PV-positive neurons in pain regulation was studied using chemogenetics based on designer receptors exclusively activated by designer drugs (DREADD). Then, projections from the TRNrd PV-positive neurons were explored using PV-Cre transgenic mice, conditional anterograde axonal tract tracing, and optogenetics, combined with immunohistochemistry and electrophysiology. The results showed that activation of PV-positive neurons in the TRNrd decreased the mechanical threshold and thermal latency of behaving mice during the light period when neuronal activity was low. Furthermore, the anterodorsal and paratenial thalamic nucleus received innervation from PV-positive neurons in the TRNrd. They were specifically inhibited by GABA, which is released from local axonal endings of PV neurons. These findings indicate that activation of PV neurons in the TRNrd increases pain sensitivity in PV-Cre transgenic mice., (Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2017
- Full Text
- View/download PDF
40. Dietary Zinc Acts as a Sleep Modulator.
- Author
-
Cherasse Y and Urade Y
- Subjects
- Animals, Dietary Supplements, Humans, Sleep Aids, Pharmaceutical administration & dosage, Sleep Aids, Pharmaceutical pharmacology, Zinc administration & dosage, Zinc pharmacology, Sleep drug effects, Zinc metabolism
- Abstract
While zinc is known to be important for many biological processes in animals at a molecular and physiological level, new evidence indicates that it may also be involved in the regulation of sleep. Recent research has concluded that zinc serum concentration varies with the amount of sleep, while orally administered zinc increases the amount and the quality of sleep in mice and humans. In this review, we provide an exhaustive study of the literature connecting zinc and sleep, and try to evaluate which molecular mechanism is likely to be involved in this phenomenon. A better understanding should provide critical information not only about the way zinc is related to sleep but also about how sleep itself works and what its real function is., Competing Interests: The authors declare no conflict of interest.
- Published
- 2017
- Full Text
- View/download PDF
41. Striatal adenosine A 2A receptor neurons control active-period sleep via parvalbumin neurons in external globus pallidus.
- Author
-
Yuan XS, Wang L, Dong H, Qu WM, Yang SR, Cherasse Y, Lazarus M, Schiffmann SN, d'Exaerde AK, Li RX, and Huang ZL
- Subjects
- Adenosine metabolism, Animals, Brain Mapping, Male, Mice, Microscopy, Immunoelectron, Neurons chemistry, Globus Pallidus physiology, Neostriatum physiology, Neurons physiology, Parvalbumins analysis, Receptor, Adenosine A2A analysis, Sleep, Wakefulness
- Abstract
Dysfunction of the striatum is frequently associated with sleep disturbances. However, its role in sleep-wake regulation has been paid little attention even though the striatum densely expresses adenosine A
2A receptors (A2A Rs), which are essential for adenosine-induced sleep. Here we showed that chemogenetic activation of A2A R neurons in specific subregions of the striatum induced a remarkable increase in non-rapid eye movement (NREM) sleep. Anatomical mapping and immunoelectron microscopy revealed that striatal A2A R neurons innervated the external globus pallidus (GPe) in a topographically organized manner and preferentially formed inhibitory synapses with GPe parvalbumin (PV) neurons. Moreover, lesions of GPe PV neurons abolished the sleep-promoting effect of striatal A2A R neurons. In addition, chemogenetic inhibition of striatal A2A R neurons led to a significant decrease of NREM sleep at active period, but not inactive period of mice. These findings reveal a prominent contribution of striatal A2A R neuron/GPe PV neuron circuit in sleep control.- Published
- 2017
- Full Text
- View/download PDF
42. Slow-wave sleep is controlled by a subset of nucleus accumbens core neurons in mice.
- Author
-
Oishi Y, Xu Q, Wang L, Zhang BJ, Takahashi K, Takata Y, Luo YJ, Cherasse Y, Schiffmann SN, de Kerchove d'Exaerde A, Urade Y, Qu WM, Huang ZL, and Lazarus M
- Subjects
- Animals, Circadian Rhythm, Female, Male, Mice, Mice, Inbred C57BL, Motivation, Patch-Clamp Techniques, Proto-Oncogene Proteins c-fos metabolism, Receptor, Adenosine A2A metabolism, Receptor, Adenosine A2A physiology, Nucleus Accumbens physiology, Sleep physiology
- Abstract
Sleep control is ascribed to a two-process model, a widely accepted concept that posits homoeostatic drive and a circadian process as the major sleep-regulating factors. Cognitive and emotional factors also influence sleep-wake behaviour; however, the precise circuit mechanisms underlying their effects on sleep control are unknown. Previous studies suggest that adenosine has a role affecting behavioural arousal in the nucleus accumbens (NAc), a brain area critical for reinforcement and reward. Here, we show that chemogenetic or optogenetic activation of excitatory adenosine A
2A receptor-expressing indirect pathway neurons in the core region of the NAc strongly induces slow-wave sleep. Chemogenetic inhibition of the NAc indirect pathway neurons prevents the sleep induction, but does not affect the homoeostatic sleep rebound. In addition, motivational stimuli inhibit the activity of ventral pallidum-projecting NAc indirect pathway neurons and suppress sleep. Our findings reveal a prominent contribution of this indirect pathway to sleep control associated with motivation.In addition to circadian and homoeostatic drives, motivational levels influence sleep-wake cycles. Here the authors demonstrate that adenosine receptor-expressing neurons in the nucleus accumbens core that project to the ventral pallidum are inhibited by motivational stimuli and are causally involved in the control of slow-wave sleep.- Published
- 2017
- Full Text
- View/download PDF
43. Natural (∆ 9 -THC) and synthetic (JWH-018) cannabinoids induce seizures by acting through the cannabinoid CB 1 receptor.
- Author
-
Malyshevskaya O, Aritake K, Kaushik MK, Uchiyama N, Cherasse Y, Kikura-Hanajiri R, and Urade Y
- Subjects
- Animals, Dose-Response Relationship, Drug, Electroencephalography, Electromyography, Locomotion, Mice, Piperidines pharmacology, Pyrazoles pharmacology, Receptor, Cannabinoid, CB1 antagonists & inhibitors, Seizures physiopathology, Dronabinol adverse effects, Indoles adverse effects, Naphthalenes adverse effects, Receptor, Cannabinoid, CB1 metabolism, Seizures etiology, Seizures metabolism
- Abstract
Natural cannabinoids and their synthetic substitutes are the most widely used recreational drugs. Numerous clinical cases describe acute toxic symptoms and neurological consequences following inhalation of the mixture of synthetic cannabinoids known as "Spice." Here we report that an intraperitoneal administration of the natural cannabinoid Δ
9 -tetrahydrocannabinol (10 mg/kg), one of the main constituent of marijuana, or the synthetic cannabinoid JWH-018 (2.5 mg/kg) triggered electrographic seizures in mice, recorded by electroencephalography and videography. Administration of JWH-018 (1.5, 2.5 and 5 mg/kg) increased seizure spikes dose-dependently. Pretreatment of mice with AM-251 (5 mg/kg), a cannabinoid receptor 1-selective antagonist, completely prevented cannabinoid-induced seizures. These data imply that abuse of cannabinoids can be dangerous and represents an emerging public health threat. Additionally, our data strongly suggest that AM-251 could be used as a crucial prophylactic therapy for cannabinoid-induced seizures or similar life-threatening conditions.- Published
- 2017
- Full Text
- View/download PDF
44. Activation of ventral tegmental area dopamine neurons produces wakefulness through dopamine D 2 -like receptors in mice.
- Author
-
Oishi Y, Suzuki Y, Takahashi K, Yonezawa T, Kanda T, Takata Y, Cherasse Y, and Lazarus M
- Subjects
- Animals, Behavior, Animal drug effects, Dopamine D2 Receptor Antagonists pharmacology, Dopamine Plasma Membrane Transport Proteins deficiency, Dopamine Plasma Membrane Transport Proteins genetics, Dopaminergic Neurons drug effects, Electroencephalography, Electromyography, Genotype, Mice, Knockout, Phenotype, Proto-Oncogene Proteins c-fos metabolism, Receptors, Dopamine D3 metabolism, Substantia Nigra drug effects, Substantia Nigra metabolism, Time Factors, Ventral Tegmental Area drug effects, Dopaminergic Neurons metabolism, Receptors, Dopamine D2 metabolism, Ventral Tegmental Area metabolism, Wakefulness drug effects
- Abstract
A growing body of evidence suggests that dopamine plays a role in sleep-wake regulation, but the dopamine-producing brain areas that control sleep-wake states are unclear. In this study, we chemogenetically activated dopamine neurons in the ventral midbrain of mice to examine the role of these neurons in sleep-wake regulation. We found that activation of dopamine neurons in the ventral tegmental area (VTA), but not in the substantia nigra, strongly induced wakefulness, although both cell populations expressed the neuronal activity marker c-Fos after chemogenetic stimulation. Analysis of the pattern of behavioral states revealed that VTA activation increased the duration of wakefulness and decreased the number of wakefulness episodes, indicating that wakefulness was consolidated by VTA activation. The increased wakefulness evoked by VTA activation was completely abolished by pretreatment with the dopamine D
2 /D3 receptor antagonist raclopride, but not by the D1 receptor antagonist SCH23390. These findings indicate that the activation of VTA dopamine neurons promotes wakefulness via D2 /D3 receptors.- Published
- 2017
- Full Text
- View/download PDF
45. Zinc-rich oysters as well as zinc-yeast- and astaxanthin-enriched food improved sleep efficiency and sleep onset in a randomized controlled trial of healthy individuals.
- Author
-
Saito H, Cherasse Y, Suzuki R, Mitarai M, Ueda F, and Urade Y
- Subjects
- Actigraphy, Adult, Aged, Aged, 80 and over, Animals, Antioxidants pharmacology, Cholesterol blood, Diet, Diet Records, Dietary Supplements, Double-Blind Method, Female, Humans, Male, Middle Aged, Surveys and Questionnaires, Xanthophylls pharmacology, Young Adult, Zinc blood, Food, Fortified, Ostreidae chemistry, Saccharomyces cerevisiae, Seafood analysis, Sleep drug effects, Zinc pharmacology
- Abstract
Scope: Zinc is an essential mineral that plays an important role in the body. We previously reported that orally feeding zinc-enriched yeast to mice induces nonrapid-eye-movement sleep. In addition, astaxanthin, an antioxidant abundant in seafood such as salmon and krill, is able to chelate minerals and may promote zinc absorption, which in return may also improve sleep. The purpose of our study was to examine the effect of zinc-rich and astaxanthin-containing food on sleep in humans., Methods and Results: We conducted a randomized, double-blinded, placebo-controlled parallel group trial of 120 healthy subjects and recorded their night activity by actigraphy for 12 weeks. These subjects were divided into four groups: placebo, zinc-rich food, zinc-, and astaxanthin-rich food, and placebo supplemented with zinc-enriched yeast and astaxanthin oil. Compared with the placebo group, the zinc-rich food group efficiently decreased the time necessary to fall asleep and improved sleep efficiency, whereas the group that ingested zinc-enriched yeast and astaxanthin oil significantly improved the sleep onset latency., Conclusion: Actigraphic sleep monitoring demonstrated that eating zinc-rich food improved sleep onset latency as well as improved the sleep efficiency in healthy individuals., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2017
- Full Text
- View/download PDF
46. Adenosine A 2A receptors in the olfactory bulb suppress rapid eye movement sleep in rodents.
- Author
-
Wang YQ, Li R, Wang DR, Cherasse Y, Zhang Z, Zhang MQ, Lavielle O, McEown K, Schiffmann SN, de Kerchove d'Exaerde A, Qu WM, Lazarus M, and Huang ZL
- Subjects
- Adenosine analogs & derivatives, Adenosine pharmacology, Adenosine A2 Receptor Agonists pharmacology, Adenosine A2 Receptor Antagonists pharmacology, Analysis of Variance, Animals, Dependovirus genetics, Dose-Response Relationship, Drug, Electroencephalography, Electromyography, Luminescent Proteins genetics, Luminescent Proteins metabolism, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Neural Inhibition drug effects, Neural Inhibition genetics, Olfactory Bulb drug effects, Patch-Clamp Techniques, Phenethylamines pharmacology, Proto-Oncogene Proteins c-fos metabolism, Pyrimidines pharmacology, RNA, Small Interfering genetics, RNA, Small Interfering metabolism, Rats, Rats, Sprague-Dawley, Receptor, Adenosine A2A genetics, Sleep, REM genetics, Transduction, Genetic, Triazoles pharmacology, Olfactory Bulb physiology, Receptor, Adenosine A2A metabolism, Sleep, REM physiology
- Abstract
Rapid eye movement (REM) sleep behavior disorder in humans is often accompanied by a reduced ability to smell and detect odors, and olfactory bulbectomized rats exhibit increased REM sleep, suggesting that the olfactory bulb (OB) is involved in REM-sleep regulation. However, the molecular mechanism of REM-sleep regulation by the OB is unknown. Adenosine promotes sleep and its A
2A receptors (A2A R) are expressed in the OB. We hypothesized that A2A R in the OB regulate REM sleep. Bilateral microinjections of the A2A R antagonist SCH58261 into the rat OB increased REM sleep, whereas microinjections of the A2A R agonist CGS21680 decreased REM sleep. Similar to the A2A R antagonist, selective A2A R knockdown by adeno-associated virus carrying short-hairpin RNA for A2A R in the rat OB increased REM sleep. Using chemogenetics on the basis of designer receptors exclusively activated by designer drugs, we demonstrated that the inhibition of A2A R neurons increased REM sleep, whereas the activation of these neurons decreased REM sleep. Moreover, using a conditional anterograde axonal tract-tracing approach, we found that OB A2A R neurons innervate the piriform cortex and olfactory tubercle. These novel findings indicate that adenosine suppresses REM sleep via A2A R in the OB of rodents.- Published
- 2017
- Full Text
- View/download PDF
47. Chemogenetic inhibition of the medial prefrontal cortex reverses the effects of REM sleep loss on sucrose consumption.
- Author
-
McEown K, Takata Y, Cherasse Y, Nagata N, Aritake K, and Lazarus M
- Subjects
- Animals, Chloride Channels genetics, Chloride Channels metabolism, Glutamates metabolism, Ivermectin metabolism, Male, Mice, Inbred C57BL, Recombinant Proteins genetics, Recombinant Proteins metabolism, Appetite Regulation, Prefrontal Cortex physiology, Sleep, REM, Sucrose metabolism, Sweetening Agents metabolism
- Abstract
Rapid eye movement (REM) sleep loss is associated with increased consumption of weight-promoting foods. The prefrontal cortex (PFC) is thought to mediate reward anticipation. However, the precise role of the PFC in mediating reward responses to highly palatable foods (HPF) after REM sleep deprivation is unclear. We selectively reduced REM sleep in mice over a 25-48 hr period and chemogenetically inhibited the medial PFC (mPFC) by using an altered glutamate-gated and ivermectin-gated chloride channel that facilitated neuronal inhibition through hyperpolarizing infected neurons. HPF consumption was measured while the mPFC was inactivated and REM sleep loss was induced. We found that REM sleep loss increased HPF consumption compared to control animals. However, mPFC inactivation reversed the effect of REM sleep loss on sucrose consumption without affecting fat consumption. Our findings provide, for the first time, a causal link between REM sleep, mPFC function and HPF consumption., Competing Interests: The authors declare that no competing interests exist.
- Published
- 2016
- Full Text
- View/download PDF
48. mDia and ROCK Mediate Actin-Dependent Presynaptic Remodeling Regulating Synaptic Efficacy and Anxiety.
- Author
-
Deguchi Y, Harada M, Shinohara R, Lazarus M, Cherasse Y, Urade Y, Yamada D, Sekiguchi M, Watanabe D, Furuyashiki T, and Narumiya S
- Subjects
- Actin Cytoskeleton metabolism, Aging, Amides pharmacology, Animals, Behavior, Animal, Brain metabolism, Cells, Cultured, Formins, GABAergic Neurons metabolism, Mice, Inbred C57BL, Nucleus Accumbens metabolism, Optogenetics, Phenotype, Presynaptic Terminals drug effects, Pyridines pharmacology, Social Isolation, Ventral Tegmental Area metabolism, Actins metabolism, Anxiety metabolism, Carrier Proteins metabolism, Presynaptic Terminals metabolism, rho-Associated Kinases metabolism
- Abstract
Here, we show neuronal inactivation-induced presynaptic remodeling and involvement of the mammalian homolog of Diaphanous (mDia) and Rho-associated coiled-coil-containing kinase (ROCK), Rho-regulated modulators of actin and myosin, in this process. We find that social isolation induces inactivation of nucleus accumbens (NAc) neurons associated with elevated anxiety-like behavior, and that mDia in NAc neurons is essential in this process. Upon inactivation of cultured neurons, mDia induces circumferential actin filaments around the edge of the synaptic cleft, which contract the presynaptic terminals in a ROCK-dependent manner. Social isolation induces similar mDia-dependent presynaptic contraction at GABAergic synapses from NAc neurons in the ventral tegmental area (VTA) associated with reduced synaptic efficacy. Optogenetic stimulation of NAc neurons rescues the anxiety phenotype, and injection of a specific ROCK inhibitor, Y-27632, into the VTA reverses both presynaptic contraction and the behavioral phenotype. mDia-ROCK signaling thus mediates actin-dependent presynaptic remodeling in inactivated NAc neurons, which underlies synaptic plasticity in emotional behavioral responses., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2016
- Full Text
- View/download PDF
49. Basal Forebrain Cholinergic Neurons Primarily Contribute to Inhibition of Electroencephalogram Delta Activity, Rather Than Inducing Behavioral Wakefulness in Mice.
- Author
-
Chen L, Yin D, Wang TX, Guo W, Dong H, Xu Q, Luo YJ, Cherasse Y, Lazarus M, Qiu ZL, Lu J, Qu WM, and Huang ZL
- Subjects
- Animals, Basal Forebrain cytology, Cerebral Cortex cytology, Cholinergic Neurons cytology, Electroencephalography, Male, Mice, Mice, Transgenic, Neural Pathways cytology, Neural Pathways physiology, Sleep Stages, Basal Forebrain physiology, Cholinergic Neurons physiology, Delta Rhythm, Sleep, Wakefulness
- Abstract
The basal forebrain (BF) cholinergic neurons have long been thought to be involved in behavioral wakefulness and cortical activation. However, owing to the heterogeneity of BF neurons and poor selectivity of traditional methods, the precise role of BF cholinergic neurons in regulating the sleep-wake cycle remains unclear. We investigated the effects of cell-selective manipulation of BF cholinergic neurons on the sleep-wake behavior and electroencephalogram (EEG) power spectrum using the pharmacogenetic technique, the 'designer receptors exclusively activated by designer drugs (DREADD)' approach, and ChAT-IRES-Cre mice. Our results showed that activation of BF cholinergic neurons expressing hM3Dq receptors significantly and lastingly decreased the EEG delta power spectrum, produced low-delta non-rapid eye movement sleep, and slightly increased wakefulness in both light and dark phases, whereas inhibition of BF cholinergic neurons expressing hM4Di receptors significantly increased EEG delta power spectrum and slightly decreased wakefulness. Next, the projections of BF cholinergic neurons were traced by humanized Renilla green fluorescent protein (hrGFP). Abundant and highly dense hrGFP-positive fibers were observed in the secondary motor cortex and cingulate cortex, and sparse hrGFP-positive fibers were observed in the ventrolateral preoptic nucleus, a known sleep-related structure. Finally, we found that activation of BF cholinergic neurons significantly increased c-Fos expression in the secondary motor cortex and cingulate cortex, but decreased c-Fos expression in the ventrolateral preoptic nucleus. Taken together, these findings reveal that the primary function of BF cholinergic neurons is to inhibit EEG delta activity through the activation of cerebral cortex, rather than to induce behavioral wakefulness.
- Published
- 2016
- Full Text
- View/download PDF
50. Zinc-containing yeast extract promotes nonrapid eye movement sleep in mice.
- Author
-
Cherasse Y, Saito H, Nagata N, Aritake K, Lazarus M, and Urade Y
- Subjects
- Administration, Oral, Animals, Dose-Response Relationship, Drug, Electroencephalography, Male, Mice, Inbred C57BL, Sleep physiology, Sleep, REM drug effects, Eye Movements drug effects, Sleep drug effects, Yeasts chemistry, Zinc pharmacology
- Abstract
Zinc is an essential trace element for humans and animals, being located, among other places, in the synaptic vesicles of cortical glutamatergic neurons and hippocampal mossy fibers in the brain. Extracellular zinc has the potential to interact with and modulate many different synaptic targets, including glutamate and GABA receptors. Because of the central role of these neurotransmitters in brain activity, we examined in this study the sleep-promoting activity of zinc by monitoring locomotor activity and electroencephalogram after its administration to mice. Zinc-containing yeast extract (40 and 80 mg/kg) dose dependently increased the total amount of nonrapid eye movement sleep and decreased the locomotor activity. However, this preparation did not change the amount of rapid eye movement sleep or show any adverse effects such as rebound of insomnia during a period of 24 h following the induction of sleep; whereas the extracts containing other divalent cations (manganese, iron, and copper) did not decrease the locomotor activity. This is the first evidence that zinc can induce sleep. Our data open the way to new types of food supplements designed to improve sleep., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2015
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.