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bioRxiv · 10.1101/2023.06.20.545788

Structural neuroplasticity after sleep loss modifies behavior and requires neurexin and neuroligin

Cowen, M. H.·Raizen, D. M.·Hart, M. P.
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Abstract

Sleep is conserved across species, and alterations in sleep are associated with a multitude of neurologic conditions. Structural neuroplasticity, or changes in the size, strength, number, and targets of neuronal synaptic connections, can be modified by sleep and sleep disruption. However, the causal relationships between sleep loss and neuroplasticity, behavioral impacts, and genetic perturbations are poorly understood. The C. elegans GABAergic DVB neuron undergoes structural plasticity in adult males that rewires synaptic connections and alters behavior; the rewiring is dependent on the conserved autism-associated genes NRXN1/nrx-1 and NLGN3/nlg-1. Stress exposure during sexual maturation, which overlaps with a developmental sleep period, alters DVB structural plasticity in early adulthood. Here, we use four distinct methods to ask whether sleep deprivation results in altered structural and behavioral plasticity of the DVB neuron. Following sleep deprivation using the genetic mutants (aptf-1 and npr-1), vibration stimulus, or chemo-genetic silencing of a sleep-producing neuron, we find that DVB neurite outgrowth at day 1 of adulthood. Sleep deprivation also leads to an increase in the time to spicule protraction, the behavioral output of DVB function. We find that nrx-1 and nlg-1 both function to regulate sleep loss induced DVB structural and functional changes. Lastly, differences in DVB neurite outgrowth in sleep deprived animals at day 1 are transient, with DVB morphology being indistinguishable from controls by day 3. These results show that sleep loss modifies DVB structural plasticity and its behavioral consequences. Further, we show nrx-1 and nlg-1 mediate the effect of sleep deprivation on behavior at the level of DVB structural plasticity. These insights into sleep, neuroplasticity, behavior, and conserved autism genes have important implications for the role of sleep in neurologic disease. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=128 SRC="FIGDIR/small/545788v1_figu1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@2320c4org.highwire.dtl.DTLVardef@3c3b86org.highwire.dtl.DTLVardef@67dc96org.highwire.dtl.DTLVardef@c3033d_HPS_FORMAT_FIGEXP M_FIG Graphical AbstractGABAergic morphologic and behavioral plasticity induced by developmental sleep deprivation depends on the conserved autism genes, nrx-1 and nlg-1 A) Sleep depriving male C. elegans during all larval sleep periods in development (aptf-1 or npr-1) or selectively inhibiting sleep during L4-adult molt (vibration or RIS silencing) results in an increase in DVB outgrowth. B) Mutations in nrx-1 (and nlg-1 in npr-1 animals) prevent sleep deprivation induced morphologic plasticity changes. C) DVB neurite outgrowth results in a functional change in spicule protraction rate as a result of increased GABAergic inhibitory signaling, which also depends on nrx-1 and nlg-1. C_FIG

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Cowen, M. H., Raizen, D. M., Hart, M. P.. 2023-06-24. Structural neuroplasticity after sleep loss modifies behavior and requires neurexin and neuroligin. https://doi.org/10.1101/2023.06.20.545788

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