International Institute for Integrative Sleep Medicine, University of TsukubaAbstract筑波大学 国際統合睡眠医科学研究機構 史研究室― 118 ―The sleep-wake cycle involves distinct changes in neural activity. During NREM sleep, the cerebral cortex exhibits slow waves characterized by delta frequency and high-amplitude EEG, alternating between depolarized up states and hyperpolarized down states. Wakefulness features a depolarized, asynchronous firing pattern with high-frequency, low-amplitude EEG. High sleep pressure increases delta wave amplitude during NREM sleep, making delta power an indicator of sleep pressure. This increase in delta power corresponds to more down states at the neuronal population level, possibly driven by delayed-activation potassium channels. Additionally, prolonged wakefulness is associated with increased dendritic spine density in the cortex, indicating that excitatory synapse strength may contribute to sleep pressure. Molecular contributors like CaMKII and SIK3 have also been identified. Understanding sleep pressure requires linking phosphorylation, synaptic strength, down states, and delta power. The relationship between increased excitatory synapse strength and electrophysiological changes such as down states and delta power remains unclear. In this study, we used a mathematical model to explore this contradiction, developing an excitatory-inhibitory neuronal network model. Our results showed that increasing synaptic strength destabilized the depolarized up state, inducing the hyperpolarized down state through a Hopf bifurcation, thus linking synaptic strength with up-down states. Finally, we altered synaptic strength in mice to study its relationship with sleep. Using a newly developed synaptic potentiation tool, SYNCit-K, to enhance synapses in the prefrontal cortex, we found that this increased delta waves and NREM sleep duration in mice. These findings provide the first evidence of a causal relationship between synaptic strength, down states, and delta waves.睡眠覚醒サイクルと記憶形成の機能的接合点の探索of Sleep-Wake Cycles and Memory FormationInvestigating the Functional Intersection 史 蕭逸Shoi Shi
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