Ultrastructural evidence for synaptic scaling across the wake/sleep cycle

Area of Science:

• Neuroscience
• Cellular Biology
• Sleep Research

Background:

• Synaptic plasticity, involving strengthening and weakening, is crucial for learning and memory.
• Existing models suggest a balance between potentiation (strengthening) and depression (weakening) to prevent memory interference.
• Energetic and informational constraints propose that potentiation occurs during wakefulness and depression during sleep.

Purpose of the Study:

• To investigate the role of sleep in regulating synaptic strength and plasticity.
• To test the hypothesis that sleep serves to renormalize synaptic potentiation accumulated during wakefulness.

Main Methods:

• Utilized three-dimensional electron microscopy to analyze 6920 synapses in mouse motor and sensory cortices.
• Measured the axon-spine interface (ASI) and spine head volume in synapses after periods of wake and sleep.

Main Results:

• The axon-spine interface (ASI) decreased by approximately 18% after sleep compared to wakefulness.
• Synaptic scaling was proportional to ASI size, indicating a size-dependent renormalization process.
• Larger synapses lacking recycling endosomes were selectively spared from scaling, suggesting a distinction between plastic and stable synapses.

Conclusions:

• Sleep plays a critical role in renormalizing overall synaptic strength that increases during wakefulness.
• Synaptic scaling during sleep selectively impacts weaker, more plastic synapses, preserving stronger, more stable ones.
• These findings support the hypothesis that sleep is essential for maintaining synaptic homeostasis and preventing memory interference.