Mechanisms of sleep and circadian ontogeny through the lens of neurodevelopmental disorders.

Highlights • Sleep and circadian disruption are highly regulated during development. • The ontogeny of sleep architecture and physiology correlates with major maturational trajectories for synapses. • Sleep dysfunction is common in neurodevelopmental disorders. • Models of neurodevelopmental disorders can shed light on the physiology of sleep and circadian rhythms. Abstract Sleep is a mysterious, developmentally regulated behavior fundamental for cognition in both adults and developing animals. A large number of studies offer a substantive body of evidence that demonstrates that the ontogeny of sleep architecture parallels brain development. Sleep deprivation impairs the consolidation of learned tasks into long-term memories and likely links sleep to the neural mechanisms underlying memory and its physiological roots in brain plasticity. Consistent with this notion is the alarming frequency of sleep and circadian rhythm dysfunction in children with neurodevelopmental disorders (NDDs). While the mechanisms underlying sleep dysfunction in most NDDs still remains poorly understood, here we will review several sentinel examples of monogenetic NDDs with both well-established connections to synaptic dysfunction and evidence of sleep or circadian dysfunction: Tuberous Sclerosis Complex, Fragile X Syndrome, and Angelman Syndrome. We suggest that the coincident maturation of sleep with synaptic physiology is one of the core reasons for the commonplace disruption of sleep in NDDs and argue that disorders with well-defined molecular genetics can provide a unique lens for understanding and unraveling the molecular correlates that link the development of sleep and circadian rhythms to health and disease. [ABSTRACT FROM AUTHOR]