All animals appear to sleep for varying durations. In humans, sleep duration changes over our lifetime, gradually reducing from birth through to old age. The mammalian body appears to use time spent asleep to recover from the effects of daily life, such as removing waste products from the brain and restoring the immune system, and may use the time to process experiences and lay down long-term memories.

However, the fundamental reasons for sleep and the mechanisms by which sleep duration is regulated remain largely unknown.

Researchers developed a computational model of sleep, based on which they predicted that sleep duration is regulated by calcium and identified multiple genes that were potentially involved. The research group then tested their predictions against 21 different genetically modified mouse types to reveal that a mechanism regulated by calcium ions is indeed responsible for controlling sleep duration.

The research group applied an efficient type of the CRISPR method developed in earlier research to remove genes involved in calcium regulation to create 21 genetically modified mice. Out of the 21, seven exhibited significant changes in sleep duration.

Authors found that impaired Ca²⁺-dependent K⁺ channels (Kcnn2 and Kcnn3), voltage-gated Ca²⁺channels (Cacna1g and Cacna1h), or Ca²⁺/calmodulin-dependent kinases (Camk2a and Camk2b) decrease sleep duration, while impaired plasma membrane Ca²⁺ATPase (Atp2b3) increases sleep duration.

In addition, the research group also showed that the inflow of calcium ions into neurons is required for mice to fall asleep and that pumping calcium ions out of neurons is required for mice to wake up. Pharmacological intervention and whole-brain imaging validated that impaired NMDA receptors reduce sleep duration and directly increase the excitability of cells. 

These results were in line with their predictions from the computational model.

http://www.riken.jp/en/pr/press/2016/20160318_2/