Cognitive hyperplasticity drives insomnia

Abstract

AbstractSleep is vital for maintenance of cognitive functions and lifespan across the animal kingdom. Here, we report our surprising findings that insomniac (inc)Drosophilashort sleep mutants, which lack a crucial adaptor protein for the autism-associated Cullin-3 ubiquitin ligase, exhibited excessive olfactory memory. Through a genetic modifier screen, we find that a mild attenuation of Protein Kinase A (PKA) signaling specifically rescued the sleep and longevity phenotypes ofincmutants. Surprisingly, this mild PKA signaling reduction further boosted the excessive memory inincmutants, coupled with further exaggerated mushroom body overgrowth phenotypes. We propose that an intrinsic hyperplasticity scenario genuine toincmutants enhances cognitive functions. Elevating PKA signaling seems to serve as a checkpoint which allows to constrain the excessive memory and mushroom body overgrowth in these animals, albeit at the sacrifice of sleep and longevity. Our data offer a mechanistic explanation for the sleep deficits ofincmutants, which challenges traditional views on the relation between sleep and memory, and suggest that behavioral hyperplasticity, e.g., prominent in autistic patients, can provoke sleep deficits.