Autism spectrum is characterized by altered social and repeated/repetitive behaviors, but also often presents with disrupted sleep behavior, such as late-onset or fragmented sleep. Furthermore, autism and other neurodevelopmental disorders have been linked to changes in synaptic plasticity and excitatory/inhibitory balance, which may mechanistically link sleep phenotypes and other behaviors in these conditions. Still, how genes associated with autism, including those that regulate synaptic function, contribute to plasticity, behavior, and sleep, remains elusive. Previous work from our lab found that the GABAergic DVB neuron undergoes morphologic plasticity in response to experiences during development and in adulthood (e.g., mating, environmental stressors). Here, we utilized genetic, chemogenetic, physical methods to disrupt sleep states in larval development in male C. elegans, and quantified DVB neuronal morphology in early adulthood. We found that all methods used to disrupt sleep led to increased DVB neurite outgrowth compared to males with normal sleep. Disruption of sleep specifically during sexual maturation (L4) was sufficient to alter DVB neuronal morphology. Using this novel model of sleep-dependent plasticity, we investigated the role of autism-associated genes in DVB plasticity in response to sleep disruption. We tested the effect of loss of function mutations in the singular C. elegans orthologs of the autism-associated genes
nrx-1/NRXN1 and
nlg-1/NLGN3 on DVB plasticity following sleep disruption. Sleep disruption in males mutant for
nrx-1 and
nlg-1 did not show altered DVB outgrowth, suggesting a role for autism-associated synaptic adhesion molecules in regulating sleep-dependent neuronal plasticity. We are currently testing in which neurons
nrx-1 and
nlg-1 are required to restore DVB plasticity after sleep disruption, and whether unique molecular mechanisms underlie the contribution of these genes in sleep-dependent plasticity. This work leverages a simple neuronal system to better define the relationship between sleep disruption, synaptic adhesion molecules, neuronal plasticity, and autism-associated genes, which has important implications for behavior and for the manifestation of neurodevelopmental conditions.