The intersection of sleep and synaptic translation in synaptic plasticity deficits in neurodevelopmental disorders

Individuals with neurodevelopmental disorders experience persistent sleep deficits, and there is increasing evidence that sleep dysregulation is an underlying cause, rather than merely an effect, of the synaptic and behavioral defects observed in these disorders. At the molecular level, dysregulation of the synaptic proteome is a common feature of neurodevelopmental disorders, though the mechanism connecting these molecular and behavioral phenotypes is an ongoing area of investigation. A role for eIF2α in shifting the local proteome in response to changes in the conditions at the synapse has emerged. Here, we discuss recent progress in characterizing the intersection of local synaptic translation and sleep and propose a reciprocal mechanism of dysregulation in the development of synaptic plasticity defects in neurodevelopmental disorders.