A design principle of spindle oscillations in mammalian sleep

Tetsuya Yamada; Shoi Shi; Hiroki R Ueda

doi:10.1016/j.isci.2022.103873

A design principle of spindle oscillations in mammalian sleep

iScience. 2022 Feb 5;25(3):103873. doi: 10.1016/j.isci.2022.103873. eCollection 2022 Mar 18.

Authors

Tetsuya Yamada^{1

2}, Shoi Shi^{2

3}, Hiroki R Ueda^{2

3}

Affiliations

¹ Faculty of Medicine, The University of Tokyo, 113-0033 Tokyo, Japan.
² Department of Systems Pharmacology, Graduate School of Medicine, The University of Tokyo, 113-0033 Tokyo, Japan.
³ Laboratory for Synthetic Biology, RIKEN Center for Biosystems Dynamics Research, 565-0871 Osaka, Japan.

Abstract

Neural oscillations are mainly regulated by molecular mechanisms and network connectivity of neurons. Large-scale simulations of neuronal networks have driven the population-level understanding of neural oscillations. However, cell-intrinsic mechanisms, especially a design principle, of neural oscillations remain largely elusive. Herein, we developed a minimal, Hodgkin-Huxley-type model of groups of neurons to investigate molecular mechanisms underlying spindle oscillation, which is synchronized oscillatory activity predominantly observed during mammalian sleep. We discovered that slowly inactivating potassium channels played an essential role in characterizing the firing pattern. The detailed analysis of the minimal model revealed that leak sodium and potassium channels, which controlled passive properties of the fast variable (i.e., membrane potential), competitively regulated the base value and time constant of the slow variable (i.e., cytosolic calcium concentration). Consequently, we propose a theoretical design principle of spindle oscillations that may explain intracellular mechanisms behind the flexible control over oscillation density and calcium setpoint.

Keywords: Complex system biology; Computer modeling; Neuroscience.