Sensory-sleep dysfunction is a shared phenotype across genetically distinct neurodevelopmental disorder models

Abstract

Sensory abnormalities and sleep disruption frequently co-occur in neurodevelopmental disorders (NDDs), but how sensory input interacts with sleep regulation in NDDs remains poorly understood. Here, we examined vibration-induced sleep (VIS), in which prolonged gentle vibration promotes sleep in Drosophila, in three genetically distinct NDD models: dNf1, dNrx1, and dFmr1. Despite markedly different baseline sleep phenotypes, all three mutants exhibited impaired VIS, identifying disrupted sensory-sleep integration as a shared phenotype across these NDD models. Behavioral responses to vibration, activity-associated CRTC signaling in Nanchung-positive (Nan+) mechanosensory neurons, and thermogenetic activation of Nan+ neurons revealed distinct underlying abnormalities across the three models, indicating that disruption at different points along the sensory-sleep axis can converge on the same behavioral phenotype. The effect of mechanosensory stimulation was also strongly shaped by homeostatic sleep drive: following sleep deprivation, vibration promoted sleep in dNf1 mutants, remained ineffective in dNrx1 mutants, and opposed recovery sleep in dFmr1 mutants. Together, these findings identify impaired sensory regulation of sleep as a point of convergence across genetically distinct NDD models and demonstrate that the expression of this shared phenotype depends on internal state.