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Optogenetic Manipulation of Neural Circuits During Monitoring Sleep/wakefulness States in Mice
Published on: June 19, 2019
Calcium/calmodulin-dependent protein kinase II α and β differentially regulate mammalian sleep
Weiwen Yang1,2, Jingyi Shi2, Chenggang Li1,2
1Chinese Institute of Brain Research, Beijing (CIBR), and Chinese Institutes for Medical Research, Beijing (CIMR), Capital Medical University, Beijing, China.
Abstract:
While sleep is important, our understanding of its molecular mechanisms is limited. Over the last two decades, protein kinases including Ca2+/calmodulin-dependent protein kinase II (CaMKII) α and β have been implicated in sleep regulation. Of all the known mouse genetic mutants, the biggest changes in sleep is reported to be observed in adult mice with sgRNAs for Camk2b injected into their embryos: sleep is reduced by approximately 120 min (mins) over 24 h (hrs). We have reexamined the sleep phenotype in mice with either Camk2a or Camk2b gene knocked-out by conventional gene targetting. While the basal sleep is reduced in Camk2a knockout mice, it remains unaltered in Camk2b mutants. Knockout of either Camk2a or Camk2b reduces sleep rebound after deprivation, indicating their roles in sleep homeostasis. These results indicate the involvement of CaMKIIα in both basal sleep and sleep homeostasis while CaMKIIβ is mainly required physiologically for sleep homeostasis, serving as a stimulus for rigorous studies in the future.
Insights
Calcium/calmodulin-dependent protein kinase II alpha (CaMKIIα) influences basal sleep, while both CaMKIIα and CaMKII beta (CaMKIIβ) are vital for sleep homeostasis. Gene knockout studies reveal distinct roles for these kinases in regulating sleep patterns.
Area of Science:
- Neuroscience
- Molecular Biology
- Sleep Science
Background:
- The molecular mechanisms underlying sleep regulation are not fully understood.
- Protein kinases, specifically Ca2+/calmodulin-dependent protein kinase II (CaMKII) alpha and beta, have been previously implicated in sleep.
- Previous studies suggested significant sleep reduction in mice with Camk2b gene alteration.
Purpose of the Study:
- To re-examine the sleep phenotype in mice with targeted gene knockouts of Camk2a and Camk2b.
- To clarify the specific roles of CaMKIIα and CaMKIIβ in basal sleep and sleep homeostasis.
Main Methods:
- Generation of knockout mouse models for Camk2a and Camk2b using conventional gene targeting.
- Phenotypic analysis of sleep patterns in wild-type and knockout mice.
- Assessment of sleep rebound following sleep deprivation.
Main Results:
- Camk2a knockout mice exhibited reduced basal sleep.
- Camk2b knockout mice showed unaltered basal sleep.
- Knockout of either Camk2a or Camk2b resulted in diminished sleep rebound after deprivation.
Conclusions:
- CaMKIIα plays a role in both basal sleep regulation and sleep homeostasis.
- CaMKIIβ is primarily essential for physiological sleep homeostasis.
- These findings necessitate further investigation into the distinct functions of CaMKII isoforms in sleep.
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