Ablation of Central Serotonergic Neurons Decreased REM Sleep and Attenuated Arousal Response
Sleep/wake behavior is regulated by distinct groups of neurons, such as dopaminergic, noradrenergic, and orexinergic neurons. Although monoaminergic neurons are usually considered to be wake-promoting, the role of serotonergic neurons in sleep/wake behavior remains inconclusive because of the effect...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-08-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fnins.2018.00535/full |
| _version_ | 1811304248063819776 |
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| author | Kanako Iwasaki Haruna Komiya Miyo Kakizaki Chika Miyoshi Manabu Abe Kenji Sakimura Hiromasa Funato Hiromasa Funato Masashi Yanagisawa Masashi Yanagisawa Masashi Yanagisawa |
| author_facet | Kanako Iwasaki Haruna Komiya Miyo Kakizaki Chika Miyoshi Manabu Abe Kenji Sakimura Hiromasa Funato Hiromasa Funato Masashi Yanagisawa Masashi Yanagisawa Masashi Yanagisawa |
| author_sort | Kanako Iwasaki |
| collection | DOAJ |
| description | Sleep/wake behavior is regulated by distinct groups of neurons, such as dopaminergic, noradrenergic, and orexinergic neurons. Although monoaminergic neurons are usually considered to be wake-promoting, the role of serotonergic neurons in sleep/wake behavior remains inconclusive because of the effect of serotonin (5-HT)-deficiency on brain development and the compensation for inborn 5-HT deficiency by other sleep/wake-regulating neurons. Here, we performed selective ablation of central 5-HT neurons in the newly developed Rosa-diphtheria toxin receptor (DTR)-tdTomato mouse line that was crossed with Pet1Cre/+ mice to examine the role of 5-HT neurons in the sleep/wake behavior of adult mice. Intracerebroventricular administration of diphtheria toxin completely ablated tdTomato-positive cells in Pet1Cre/+; Rosa-DTR-tdTomato mice. Electroencephalogram/electromyogram-based sleep/wake analysis demonstrated that central 5-HT neuron ablation in adult mice decreased the time spent in rapid eye movement (REM) sleep, which was associated with fewer transitions from non-REM (NREM) sleep to REM sleep than in control mice. Central 5-HT neuron-ablated mice showed attenuated wake response to a novel environment and increased theta power during wakefulness compared to control mice. The current findings indicated that adult 5-HT neurons work to support wakefulness and regulate REM sleep time through a biased transition from NREM sleep to REM sleep. |
| first_indexed | 2024-04-13T08:03:46Z |
| format | Article |
| id | doaj.art-9d23b6934db34bdd8e81aff920c97363 |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-04-13T08:03:46Z |
| publishDate | 2018-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-9d23b6934db34bdd8e81aff920c973632022-12-22T02:55:14ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2018-08-011210.3389/fnins.2018.00535379443Ablation of Central Serotonergic Neurons Decreased REM Sleep and Attenuated Arousal ResponseKanako Iwasaki0Haruna Komiya1Miyo Kakizaki2Chika Miyoshi3Manabu Abe4Kenji Sakimura5Hiromasa Funato6Hiromasa Funato7Masashi Yanagisawa8Masashi Yanagisawa9Masashi Yanagisawa10International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, JapanInternational Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, JapanInternational Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, JapanInternational Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, JapanDepartment of Cellular Neurobiology, Brain Research Institute, Niigata University, Niigata, JapanDepartment of Cellular Neurobiology, Brain Research Institute, Niigata University, Niigata, JapanInternational Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, JapanDepartment of Anatomy, Faculty of Medicine, Toho University, Tokyo, JapanInternational Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, JapanDepartment of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX, United StatesLife Science Center, Tsukuba Advanced Research Alliance, University of Tsukuba, Tsukuba, JapanSleep/wake behavior is regulated by distinct groups of neurons, such as dopaminergic, noradrenergic, and orexinergic neurons. Although monoaminergic neurons are usually considered to be wake-promoting, the role of serotonergic neurons in sleep/wake behavior remains inconclusive because of the effect of serotonin (5-HT)-deficiency on brain development and the compensation for inborn 5-HT deficiency by other sleep/wake-regulating neurons. Here, we performed selective ablation of central 5-HT neurons in the newly developed Rosa-diphtheria toxin receptor (DTR)-tdTomato mouse line that was crossed with Pet1Cre/+ mice to examine the role of 5-HT neurons in the sleep/wake behavior of adult mice. Intracerebroventricular administration of diphtheria toxin completely ablated tdTomato-positive cells in Pet1Cre/+; Rosa-DTR-tdTomato mice. Electroencephalogram/electromyogram-based sleep/wake analysis demonstrated that central 5-HT neuron ablation in adult mice decreased the time spent in rapid eye movement (REM) sleep, which was associated with fewer transitions from non-REM (NREM) sleep to REM sleep than in control mice. Central 5-HT neuron-ablated mice showed attenuated wake response to a novel environment and increased theta power during wakefulness compared to control mice. The current findings indicated that adult 5-HT neurons work to support wakefulness and regulate REM sleep time through a biased transition from NREM sleep to REM sleep.https://www.frontiersin.org/article/10.3389/fnins.2018.00535/full5-HT neuronserotoninsleepREMSdiphtheria toxinbrain |
| spellingShingle | Kanako Iwasaki Haruna Komiya Miyo Kakizaki Chika Miyoshi Manabu Abe Kenji Sakimura Hiromasa Funato Hiromasa Funato Masashi Yanagisawa Masashi Yanagisawa Masashi Yanagisawa Ablation of Central Serotonergic Neurons Decreased REM Sleep and Attenuated Arousal Response Frontiers in Neuroscience 5-HT neuron serotonin sleep REMS diphtheria toxin brain |
| title | Ablation of Central Serotonergic Neurons Decreased REM Sleep and Attenuated Arousal Response |
| title_full | Ablation of Central Serotonergic Neurons Decreased REM Sleep and Attenuated Arousal Response |
| title_fullStr | Ablation of Central Serotonergic Neurons Decreased REM Sleep and Attenuated Arousal Response |
| title_full_unstemmed | Ablation of Central Serotonergic Neurons Decreased REM Sleep and Attenuated Arousal Response |
| title_short | Ablation of Central Serotonergic Neurons Decreased REM Sleep and Attenuated Arousal Response |
| title_sort | ablation of central serotonergic neurons decreased rem sleep and attenuated arousal response |
| topic | 5-HT neuron serotonin sleep REMS diphtheria toxin brain |
| url | https://www.frontiersin.org/article/10.3389/fnins.2018.00535/full |
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