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Kayser, M. S.

Publications and source records attributed to Kayser, M. S..

3 recordsLinked to original sources

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

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.

neuroscience

Starvation resistance is associated with developmentally specified changes in sleep, feeding and metabolic rate

Food shortage represents a primary challenge to survival, and animals have adapted diverse developmental, physiological, and behavioral strategies to survive when food becomes unavailable. Starvation resistance is strongly influenced by ecological and evolutionary history, yet the genetic basis for the evolution of starvation resistance remains poorly understood. The fruit fly, Drosophila melanogaster, provides a powerful model for leveraging experimental evolution to investigate traits associated with starvation resistance. While control populations only live a few days without food, selection for starvation resistances results in populations that can survive weeks. We have previously shown that selection for starvation resistance results in increased sleep and reduced feeding in adult flies. Here, we investigate the ontogeny of starvation resistance-associated behavioral and metabolic phenotypes in these experimentally selected flies. We find that selection for starvation resistance results in delayed development and a reduction in metabolic rate in larvae that persists into adulthood, suggesting that these traits may allow for the accumulation of energy stores and an increase in body size within these selected populations. In addition, we find that sleep is largely unaffected by starvation- selection and that feeding increases during the late larval stages, suggesting that experimental evolution for starvation resistance produces developmentally specified changes in behavioral regulation. Together, these findings reveal a critical role for development in the evolution of starvation resistance and indicate that selection can selectively influence behavior during defined developmental timepoints.\n\nSUMMARY STATEMENTDrosophila melanogaster selected for starvation resistance take longer to develop and exhibit development-specific changes in traits associated with the accumulation and conservation of energy stores.

neuroscience

A Drosophila Model for Behavioral Sleep Modification

Insomnia is the most common sleep disorder among adults, especially affecting individuals of advanced age or with neurodegenerative disease. Insomnia is also a common comorbidity across psychiatric disorders. Cognitive Behavioral Therapy for Insomnia (CBT-I) is the first-line treatment for insomnia; a key component of this intervention is restriction of sleep opportunity, which optimizes matching of sleep ability and opportunity, leading to enhanced sleep drive. Despite the well-documented efficacy of CBT-I, little is known regarding how CBT-I works at a cellular and molecular level to improve sleep, due in large part to an absence of experimentally-tractable animals models of this intervention. Here, guided by human behavioral sleep therapies, we developed a Drosophila model for behavioral modification of sleep. We demonstrate that restriction of sleep opportunity through manipulation of environmental cues improves sleep efficiency and quality in multiple short-sleeping Drosophila mutants. The response to sleep opportunity restriction requires ongoing environmental inputs, but is independent of the molecular circadian clock. We apply this sleep opportunity restriction paradigm to aging and Alzheimers disease fly models, and find that sleep impairments in these models are reversible with sleep restriction, with associated improvement in reproductive fitness and extended lifespan. This work establishes a model to investigate the neurobiological basis of CBT-I, and provides a platform that can be exploited towards novel treatment targets for insomnia.

neuroscience