Integrated Calendar

Sleep may be universal in the animal kingdom. Yet, the roles of sleep and the underlying reason for this universality remain controversial. The roundworm Caenorhabditis elegans is the simplest model system in which these questions can be addressed. This talk will describe consequences of disruptions to worm sleep, which can range from compensation for mild disruptions to long lasting ill effects of severe but nonlethal deprivation. A key feature of sleep is its intricate compensatory mechanisms: following disruptions, ‘restoring forces’ extend or modify sleep to compensate for the loss. Weak and intermediate perturbations reveal mechanistically distinct manners by which small losses of worm sleep are compensated for. Stronger perturbations, causing substantial but nonlethal sleep loss, can result in long-term deficits to neural circuits and other cell types. We found that unfolded protein responses (UPRs) were triggered by worm sleep deprivation. These protective responses are indicative of the type of damage inflicted: compromising them exacerbates the manifestations of worm fatigue. The simplicity of C. elegans enabled comparing their potential importance in different circuits and tissues. Interestingly, distinct UPRs affected different neural circuits. Therefore, worm fatigue and the mechanisms that mitigate it point to core functions of sleep in this phylogenetically ancient model organism.