While prompt sensory detection of X-rays has been documented across a wide variety of species, relatively few studies have explored the underlying molecular mechanisms of these acute sensory responses. Here we report the discovery of an acute behavioral avoidance response in wild type C. elegans to X-ray stimulation. The endogenous C. elegans photoreceptor protein LITE-1, which mediates UV-avoidance behavior, was found to also underlie a similar behavioral response to X-radiation. We observed that wild type nematodes exhibited a dramatic avoidance response to 1 Gy/s focused X-ray stimulation. The response consisted of a marked increase in activity, involving increased forward locomotion, omega bends, and reversals, observed within 2 s of stimulation onset and subsiding once the worm escaped the path of the focused X-ray beam. Moderate dose rates of 0.5 and 0.7 Gy/s evoked similar, but somewhat slower and less vigorous responses, while 0.2 Gy/s and sham (0 Gy/s) stimulation did not elicit any significant response. Nematodes with the
lite-1(
ce314) mutation, which renders LITE-1 dysfunctional, failed to exhibit the X-ray avoidance behavioral phenotype seen in wild type and
lite-1 intact mutant strains, suggesting that functional
lite-1 is critical for the X-ray avoidance response. To verify LITE-1's sensitivity to X-rays and determine whether ectopic expression of
lite-1 can confer X-ray sensitivity to otherwise X-ray insensitive cells, we administered unfocused X-ray stimulation to swimming
pmyo-3::
lite-1 worms, which transgenically express
lite-1 in myocytes. Transgenic, but not wild type, nematodes exhibited a strong paralysis response, quantified as a dramatic decrease in body bend frequency and sometimes accompanied by egg ejection, in response to the stimulation. High dose rates of 0.56 and 0.74 Gy/s produced the most extreme effects, however, paralysis responses were seen at X-ray intensities as low as 0.19 Gy/s. Together, these results suggest that LITE-1 can function as an X-ray sensitive receptor, playing a critical role in the transduction of X-ray signals into neural activity to produce behavioral responses. This is the first demonstration of X-ray based optogenetic (X-genetic) manipulation of cellular electrical activity in intact behaving animals. As such, LITE-1 shows strong potential for use in this novel method of neuromodulation to transduce transcranial X-ray signals for precise, but minimally invasive manipulation of neural activity in mammals.