Sleep promotes neuronal autophagy for intracellular clearance

Extended wakefulness in mouse cortex selectively suppresses neuronal autophagic flux, but sleep rapidly restores it and shifts cargo from mitochondrial components to synaptic proteins.

• Why it matters: Sleep’s cellular role in maintaining neuronal homeostasis is unclear, and impaired proteostasis is linked to neurodegenerative disease, motivating a brain-state–specific mechanism.
• What they did: Mice were compared across extended wakefulness versus sleep, with autophagic flux and cargo assessed in cortex; ATG7 was measured, and lysosomal acidification was manipulated using closed-loop optogenetic stimulation in 5xFAD mice.
• The result: Sleep upregulated ATG7 and supported lysosomal degradation plus a putative noncanonical secretory route; low neuronal activity supported efficient flux, while Gq activation impaired autophagy and increased intracellular amyloid-beta accumulation, and sleep-only lysosomal stimulation reduced amyloid pathology in 5xFAD mice.

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