期刊
JOURNAL OF NEUROSCIENCE
卷 42, 期 38, 页码 7244-7255出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.2288-21.2022
关键词
dorsal raphe; optogenetics; photometry; population activity; serotonin; sleep
资金
- Ministry of Education, Culture, Sports, Science, and Technology [20H05894]
- Japan Agency for Medical Research and Development [JP21dm0207069]
- Japan Society for the Promotion of Science [21H00212, 19K06944]
Dorsal raphe (DR) 5-HT neurons play a crucial role in regulating sleep-wake transitions. The activity of these neurons fluctuates during the sleep-wake cycle, with slow oscillatory signals during non-rapid eye movement (NREM) sleep and cessation during rapid eye movement (REM) sleep. The oscillatory activity of DR 5-HT neurons is associated with EEG power fluctuation, and optogenetic manipulation of these neurons can induce or prolong specific sleep states.
Dorsal raphe (DR) 5-HT neurons regulate sleep-wake transitions. Previous studies demonstrated that single-unit activity of DR 5-HT neurons is high during wakefulness, decreases during non-rapid eye movement (NREM) sleep, and ceases during rapid eye movement (REM) sleep. However, characteristics of the population-level activity of DR 5-HT neurons, which influ-ence the entire brain, are largely unknown. Here, we measured population activities of 5-HT neurons in the male and female mouse DR across the sleep-wake cycle by ratiometric fiber photometry. We found a slow oscillatory activity of compound in-tracellular Ca21 signals during NREM sleep. The trough of the concave 5-HT activity increased across sleep progression, but 5-HT activity always returned to that seen during the wake period. When the trough reached a minimum and remained there, REM sleep was initiated. We also found a unique coupling of the oscillatory 5-HT activity and wideband EEG power fluctuation. Furthermore, optogenetic activation of 5-HT neurons during NREM sleep triggered a high EMG power and induced wakefulness, demonstrating a causal role of 5-HT neuron activation. Optogenetic inhibition induced REM sleep or sustained NREM, with an EEG power increase and EEG fluctuation, and pharmacological silencing of 5-HT activity using a selective serotonin reuptake inhibitor led to sustained NREM, with an EEG power decrease and EEG fluctuation. These inhib-itory manipulations supported the association between oscillatory 5-HT activity and EEG fluctuation. We propose that NREM sleep is not a monotonous state, but rather it contains dynamic changes that coincide with the oscillatory population-level ac-tivity of DR 5-HT neurons.
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