Developing forebrain synapses are uniquely vulnerable to sleep loss.

Area of Science:

• Neuroscience
• Developmental Biology
• Sleep Science

Background:

• Sleep is crucial for brain health and cognition throughout life.
• Synapses are key targets for sleep's restorative functions and are affected by sleep deprivation (SD).
• Sleep's role in synaptic function differs between development and adulthood, with implications for neurodevelopmental disorders like autism spectrum disorder (ASD).

Purpose of the Study:

• To investigate the distinct functions of sleep and vulnerability mechanisms to SD across different developmental stages (juvenile, adolescent, adult).
• To compare the behavioral and molecular responses to acute SD in mice at P21-28, P42-49, and P70-100.

Main Methods:

• Systematic examination of behavioral and molecular responses to acute sleep deprivation.
• Utilized juvenile, adolescent, and adult mice of both sexes.
• Employed subcellular fractionation, proteome, and phosphoproteome analysis.

Main Results:

• Juvenile mice showed cognitive deficits and lacked adaptations to SD, unlike adults who exhibited resilience.
• Developing synapses were profoundly vulnerable to SD, with aberrant induction of synapse potentiation, synaptogenesis, and perineuronal net expression in juveniles.
• Adult synapses demonstrated comparative resilience to SD.

Conclusions:

• Sleep serves distinct developmental functions, with developing synapses being uniquely vulnerable to sleep disruption.
• Sleep deprivation in early life profoundly impacts brain development and synapse maturation.
• The developing synapse may be a convergence point for SD vulnerability and ASD genetic risk, offering insights into ASD susceptibility.