Stereotypical Escape Behavior in Caenorhabditis elegans Allows Quantification of Effective Heat Stimulus Level

A goal of many sensorimotor studies is to quantify the stimulus-behavioral response relation for specific organisms and specific sensory stimuli. This is especially important to do in the context of painful stimuli since most animals in these studies cannot easily communicate to us their perceived levels of such noxious stimuli. Thus progress on studies of nociception and pain-like responses in animal models depends crucially on our ability to quantitatively and objectively infer the sensed levels of these stimuli from animal behaviors. Here we develop a quantitative model to infer the perceived level of heat stimulus from the stereotyped escape response of individual nematodes Caenorhabditis elegans stimulated by an IR laser. The model provides a method for quantification of analgesic-like effects of chemical stimuli or genetic mutations in C. elegans. We test ibuprofen-treated worms and a TRPV (transient receptor potential) mutant, and we show that the perception of heat stimuli for the ibuprofen treated worms is lower than the wild-type. At the same time, our model shows that the mutant changes the worm’s behavior beyond affecting the thermal sensory system. Finally, we determine the stimulus level that best distinguishes the analgesic-like effects and the minimum number of worms that allow for a statistically significant identification of these effects.Author Summary: A doctor assesses pain by asking her patient to “rate your pain on the scale of 1 to 10.” She may then prescribe some drugs and later ask the question again to see if they worked. New drugs are often developed using animal models, but we cannot ask an animal, especially a small invertebrate animal, to rate, similarly, the strength of its perceived noxious stimulus. In this paper, we successfully develop computational tools that read the “body language” of a roundworm C. elegans to estimate the strength of the heat stimulus that it experiences. Unlike previous attempts that have focused on ad hoc selected components of the overall behavior, our approach is based on quantifying the complete time series of the escape behavior, which we show to be captured by a behavioral “template” that scales in response to the stimulus strength. The existence of this template allows us to solve one of the hard questions in pain research: disambiguating analgesic-like effects of drugs or genetic perturbations from their other effects on animal behavior.