Developing forebrain synapses are uniquely vulnerable to sleep loss

Abstract

Sleep supports lifelong brain health and cognition. Sleep loss in early life can drive lasting changes in adult behavior, indicating sleep plays a distinct but poorly understood role in brain development. We systematically examined the homeostatic adaptations and synaptic consequences of acute sleep deprivation (SD) in developing and adult mice. Developing mice lack robust homeostatic adaptations to SD, exacerbating cognitive deficits. Synapse proteome and phosphoproteome analysis revealed profound vulnerability to SD in developing mice, including immediate impacts on synaptogenesis and key aspects of brain development. With maturation, a unified biochemical effect of sleep on synapses emerges, together with robust homeostatic adaptations and resilience to SD. Our findings show sleep plays a distinct role in early life supporting synapse development, transitioning to homeostatic functions with maturation.One-Sentence SummaryEffects of sleep loss across life stages indicate sleep plays a distinct role in early life supporting synapse maturation.