AUTHOR=Cannon Kelli E. , Ranasinghe Meenakshi , Millhouse Paul W. , Roychowdhury Ayona , Dobrunz Lynn E. , Foulger Stephen H. , Gauntt David M. , Anker Jeffrey N. , Bolding Mark TITLE=LITE-1 mediates behavioral responses to X-rays in Caenorhabditis elegans JOURNAL=Frontiers in Neuroscience VOLUME=Volume 17 - 2023 YEAR=2023 URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2023.1210138 DOI=10.3389/fnins.2023.1210138 ISSN=1662-453X ABSTRACT=Rapid sensory detection of X-ray stimulation has been documented across a wide variety of species, but few studies have explored the underlying molecular mechanisms. Here we report the discovery of an acute behavioral avoidance response in wild type C. elegans to X-ray stimulation. The endogenous C. elegans UV-photoreceptor protein LITE-1 was found to mediate the locomotory avoidance response. Transgenic expression of LITE-1 in C. elegans muscle cells resulted in paralysis and egg ejection responses to X-ray stimulation, demonstrating that ectopic expression of LITE-1 can confer X-ray sensitivity to otherwise X-ray insensitive cells. This work represents the first demonstration of rapid X-ray based genetically targeted (X-genetic) manipulation of cellular electrical activity in intact behaving animals. Our findings suggest that LITE-1 has strong potential for use in this minimally invasive form of neuromodulation to transduce transcranial X-ray signals for precise manipulation of neural activity in mammals, bypassing the need for invasive surgical implants to deliver stimulation.Here we report the discovery of LITE-1 dependent behavioral responses to X-radiation. Importantly, we show that LITE-1 can confer X-ray sensitivity when transgenically expressed in otherwise X-ray insensitive cells. This is the first demonstration of acute X-ray mediated modulation of cellular electrical activity that has similar functionality to optogenetics, but avoids the need for surgical implantation of optic fibers and improves targeting capabilities.