Abstract
Details
Sleep is regulated by homeostatic processes, yet the biological basis of sleep pressure that accumulates during wakefulness, triggers sleep, and dissipates during sleep remains elusive. We explored a causal relationship between cellular synaptic strength and electroencephalography delta power indicating macro-level sleep pressure by developing a theoretical framework and a molecular tool to manipulate synaptic strength. The mathematical model predicted that increased synaptic strength promotes the neuronal “down state” and raises the delta power. Our molecular tool (synapse-targeted chemically induced translocation of Kalirin-7, SYNCit-K), which induces dendritic spine enlargement and synaptic potentiation through chemically induced translocation of protein Kalirin-7, demonstrated that synaptic potentiation of excitatory neurons in the prefrontal cortex (PFC) increases nonrapid eye movement sleep amounts and delta power. Thus, synaptic strength of PFC excitatory neurons dictates sleep pressure in mammals.
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Editor’s summary
The relationship between synaptic dynamics and sleep need is still unclear. In a mathematical model, Sawada
et al
. showed how enhanced synaptic strength can promote neuronal hyperpolarization and thus increase electroencephalography (EEG) delta power. Using a multielectrode recording system, the authors experimentally confirmed that strengthening synapses increased delta power. Applying a molecular tool for long-term potentiation (LTP) induction to prefrontal cortex excitatory neurons increased both the amount and EEG delta power of non–rapid eye movement (NREM) sleep even when daily sleep need was minimal. This tool caused an increase in spine size (structural LTP) within a physiological range. Such effects were absent in inhibitory or visual cortex neurons. Pharmacologically enhancing synaptic transmission or inhibiting long-term depression also increased both the amount and EEG delta power of NREM sleep. —Peter Stern