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Silencing of Cholinergic Basal Forebrain Neurons Using Archaerhodopsin Prolongs Slow-Wave Sleep in Mice.

Shi YF, Han Y, Su YT, Yang JH, Yu YQ - PLoS ONE (2015)

Bottom Line: However, silencing these neurons changed neither the duration of wakefulness or REM sleep, nor the probability of transitions to other sleep-wake episodes from wakefulness or REM sleep.The lost wakefulness was compensated by a delayed increase of wakefulness, so the total duration of SWS and wakefulness during 24 h was kept stable.Our results indicate that the main effect of these neurons is to terminate SWS, whereas wakefulness or REM sleep may be determined by co-operation of the cholinergic BF neurons with other arousal-sleep control systems.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurobiology and Physiology, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

ABSTRACT
The basal forebrain (BF) plays a crucial role in cortical activation. Our previous study showed that activation of cholinergic BF neurons alone is sufficient to suppress slow-wave sleep (SWS) and promote wakefulness and rapid-eye-movement (REM) sleep. However, the exact role of silencing cholinergic BF neurons in the sleep-wake cycle remains unclear. We inhibitied the cholinergic BF neurons genetically targeted with archaerhodopsin (Arch) with yellow light to clarify the role of cholinergic BF neurons in the sleep-wake cycle. Bilateral inactivation of cholinergic BF neurons genetically targeted with archaerhodopsin prolonged SWS and decreased the probability of awakening from SWS in mice. However, silencing these neurons changed neither the duration of wakefulness or REM sleep, nor the probability of transitions to other sleep-wake episodes from wakefulness or REM sleep. Furthermore, silencing these neurons for 6 h within the inactive or active period increased the duration of SWS at the expense of the duration of wakefulness, as well as increasing the number of prolonged SWS episodes (120-240 s). The lost wakefulness was compensated by a delayed increase of wakefulness, so the total duration of SWS and wakefulness during 24 h was kept stable. Our results indicate that the main effect of these neurons is to terminate SWS, whereas wakefulness or REM sleep may be determined by co-operation of the cholinergic BF neurons with other arousal-sleep control systems.

No MeSH data available.


Recombination of Ai35D and ChAT-Cre mice.(A) Diagram of heterozygous mice with conditional expression of Arch-GFP after recombination of the Stop-loxP gene and ChAT-Cre recombinase. (B) PCR analysis. Ai35D heterozygous mice had one 242-bp and one 246-bp band, while WT mice had only one 242-bp band. The positive Cre band was at 350-bp.
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pone.0130130.g001: Recombination of Ai35D and ChAT-Cre mice.(A) Diagram of heterozygous mice with conditional expression of Arch-GFP after recombination of the Stop-loxP gene and ChAT-Cre recombinase. (B) PCR analysis. Ai35D heterozygous mice had one 242-bp and one 246-bp band, while WT mice had only one 242-bp band. The positive Cre band was at 350-bp.

Mentions: To selectively express Arch in cholinergic BF neurons, we obtained ChAT-Cre/Ai35D heterozygotes (ChAT-Arch mice) by breeding Ai35D mice to ChAT-Cre mice as described in the Methods (Fig 1A). The Ai35D heterozygotes were viable and fertile. They were identified by PCR and agarose gel electrophoresis with one 242-bp band and one 246-bp band (Fig 1B). Meanwhile, we also tested for the Cre gene in the ChAT-Arch mice. The positive Cre band after electrophoresis was 350 bp (Fig 1B)


Silencing of Cholinergic Basal Forebrain Neurons Using Archaerhodopsin Prolongs Slow-Wave Sleep in Mice.

Shi YF, Han Y, Su YT, Yang JH, Yu YQ - PLoS ONE (2015)

Recombination of Ai35D and ChAT-Cre mice.(A) Diagram of heterozygous mice with conditional expression of Arch-GFP after recombination of the Stop-loxP gene and ChAT-Cre recombinase. (B) PCR analysis. Ai35D heterozygous mice had one 242-bp and one 246-bp band, while WT mice had only one 242-bp band. The positive Cre band was at 350-bp.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4495063&req=5

pone.0130130.g001: Recombination of Ai35D and ChAT-Cre mice.(A) Diagram of heterozygous mice with conditional expression of Arch-GFP after recombination of the Stop-loxP gene and ChAT-Cre recombinase. (B) PCR analysis. Ai35D heterozygous mice had one 242-bp and one 246-bp band, while WT mice had only one 242-bp band. The positive Cre band was at 350-bp.
Mentions: To selectively express Arch in cholinergic BF neurons, we obtained ChAT-Cre/Ai35D heterozygotes (ChAT-Arch mice) by breeding Ai35D mice to ChAT-Cre mice as described in the Methods (Fig 1A). The Ai35D heterozygotes were viable and fertile. They were identified by PCR and agarose gel electrophoresis with one 242-bp band and one 246-bp band (Fig 1B). Meanwhile, we also tested for the Cre gene in the ChAT-Arch mice. The positive Cre band after electrophoresis was 350 bp (Fig 1B)

Bottom Line: However, silencing these neurons changed neither the duration of wakefulness or REM sleep, nor the probability of transitions to other sleep-wake episodes from wakefulness or REM sleep.The lost wakefulness was compensated by a delayed increase of wakefulness, so the total duration of SWS and wakefulness during 24 h was kept stable.Our results indicate that the main effect of these neurons is to terminate SWS, whereas wakefulness or REM sleep may be determined by co-operation of the cholinergic BF neurons with other arousal-sleep control systems.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurobiology and Physiology, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

ABSTRACT
The basal forebrain (BF) plays a crucial role in cortical activation. Our previous study showed that activation of cholinergic BF neurons alone is sufficient to suppress slow-wave sleep (SWS) and promote wakefulness and rapid-eye-movement (REM) sleep. However, the exact role of silencing cholinergic BF neurons in the sleep-wake cycle remains unclear. We inhibitied the cholinergic BF neurons genetically targeted with archaerhodopsin (Arch) with yellow light to clarify the role of cholinergic BF neurons in the sleep-wake cycle. Bilateral inactivation of cholinergic BF neurons genetically targeted with archaerhodopsin prolonged SWS and decreased the probability of awakening from SWS in mice. However, silencing these neurons changed neither the duration of wakefulness or REM sleep, nor the probability of transitions to other sleep-wake episodes from wakefulness or REM sleep. Furthermore, silencing these neurons for 6 h within the inactive or active period increased the duration of SWS at the expense of the duration of wakefulness, as well as increasing the number of prolonged SWS episodes (120-240 s). The lost wakefulness was compensated by a delayed increase of wakefulness, so the total duration of SWS and wakefulness during 24 h was kept stable. Our results indicate that the main effect of these neurons is to terminate SWS, whereas wakefulness or REM sleep may be determined by co-operation of the cholinergic BF neurons with other arousal-sleep control systems.

No MeSH data available.