| First Author | Tatsuki F | Year | 2016 |
| Journal | Neuron | Volume | 90 |
| Issue | 1 | Pages | 70-85 |
| PubMed ID | 26996081 | Mgi Jnum | J:239492 |
| Mgi Id | MGI:5828982 | Doi | 10.1016/j.neuron.2016.02.032 |
| Citation | Tatsuki F, et al. (2016) Involvement of Ca(2+)-Dependent Hyperpolarization in Sleep Duration in Mammals. Neuron 90(1):70-85 |
| abstractText | The detailed molecular mechanisms underlying the regulation of sleep duration in mammals are still elusive. To address this challenge, we constructed a simple computational model, which recapitulates the electrophysiological characteristics of the slow-wave sleep and awake states. Comprehensive bifurcation analysis predicted that a Ca(2+)-dependent hyperpolarization pathway may play a role in slow-wave sleep and hence in the regulation of sleep duration. To experimentally validate the prediction, we generate and analyze 21 KO mice. Here we found that impaired Ca(2+)-dependent K(+) channels (Kcnn2 and Kcnn3), voltage-gated Ca(2+) channels (Cacna1g and Cacna1h), or Ca(2+)/calmodulin-dependent kinases (Camk2a and Camk2b) decrease sleep duration, while impaired plasma membrane Ca(2+) ATPase (Atp2b3) increases sleep duration. Pharmacological intervention and whole-brain imaging validated that impaired NMDA receptors reduce sleep duration and directly increase the excitability of cells. Based on these results, we propose a hypothesis that a Ca(2+)-dependent hyperpolarization pathway underlies the regulation of sleep duration in mammals. |
