Involvement of Ca2+-dependent hyperpolarization in sleep duration in mammals

Tatsuki, Fumiya, Sunagawa, Genshiro A., Shi, Shoi, Susaki, Etsuo A., Yukinaga, Hiroko, Perrin, Dimitri, Sumiyama, Kenta, Ukai-Tadenuma, Maki, Fujishima, Hiroshi, Ohno, Rei-ichiro, Tone, Daisuke, Ode, Koji L., Matsumoto, Katsuhiko, & Ueda, Hiroki R. (2016) Involvement of Ca2+-dependent hyperpolarization in sleep duration in mammals. Neuron, 90(1), pp. 70-85.

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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 Ca2+-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 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. 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 Ca2+-dependent hyperpolarization pathway underlies the regulation of sleep duration in mammals.

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ID Code: 95240
Item Type: Journal Article
Refereed: Yes
DOI: 10.1016/j.neuron.2016.02.032
ISSN: 0896-6273
Divisions: Current > Schools > School of Electrical Engineering & Computer Science
Current > QUT Faculties and Divisions > Science & Engineering Faculty
Copyright Owner: Copyright 2016 Elsevier
Copyright Statement: Licensed under the Creative Commons Attribution; Non-Commercial; No-Derivatives 4.0 International. DOI: 10.1016/j.neuron.2016.02.032
Deposited On: 28 Apr 2016 22:36
Last Modified: 20 May 2016 10:39

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