Cortical parvalbumin neurons are responsible for homeostatic sleep rebound through CaMKII activation
Kazuhiro Kon, Koji L. Ode, Tomoyuki Mano, Hiroshi Fujishima, Riina R. Takahashi, Daisuke Tone, Chika Shimizu, Shinnosuke Shiono, Saori Yada, Kyoko Matsuzawa, Shota Yoshida, Junko Yoshida Garçon, Mari Kaneko, Yuta Shinohara, Rikuhiro G. Yamada, Shoi Shi, Kazunari Miyamichi, Kenta Sumiyama, Hiroshi Kiyonari, Etsuo A. Susaki, Hiroki R. Ueda
Abstract
Abstract The homeostatic regulation of sleep is characterized by rebound sleep after prolonged wakefulness, but the molecular and cellular mechanisms underlying this regulation are still unknown. In this study, we show that Ca 2+ /calmodulin-dependent protein kinase II (CaMKII)-dependent activity control of parvalbumin (PV)-expressing cortical neurons is involved in homeostatic regulation of sleep in male mice. Prolonged wakefulness enhances cortical PV-neuron activity. Chemogenetic suppression or activation of cortical PV neurons inhibits or induces rebound sleep, implying that rebound sleep is dependent on increased activity of cortical PV neurons. Furthermore, we discovered that CaMKII kinase activity boosts the activity of cortical PV neurons, and that kinase activity is important for homeostatic sleep rebound. Here, we propose that CaMKII-dependent PV-neuron activity represents negative feedback inhibition of cortical neural excitability, which serves as the distributive cortical circuits for sleep homeostatic regulation.