Thermal pain transduction in C. elegans

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Over the last 5 years, we have studied the thermal response of C. elegans at the genetic, neuronal, and locomotory scales utilizing novel behavioral phenotyping, instrumentation, and analysis. In support of new quantitative genetics work with C. briggsae we have published a foundational report on C. briggsae spatial thermotaxis behavior showing that wild isolates wildly vary in their taxis response and their integration of thermal memory (Stegeman et al., 2012). Using a novel laser-based heating instrument, we demonstrated the power of multi-parameter phenotyping on analysis of thermal “pain” behavior of a candidate mutant strain library (Ghosh et al., 2012). We improved this instrument to programmatically stimulate parts of the worm’s body with tightly focused beams of infrared laser light, to determine the spatial receptive field of the worm’s thermal pain response. Using multi-parameter quantification of the “pain” behavior we showed that: 1) C. elegans can discriminate thermal stimuli to a precision of at least 80 microns when focused on its mid-body, 2) the neuron PVD is the sensory neuron that is required for the mid-body response, and 3) a number of genes encoding glutamate receptors and TRPV-like channels are likely involved in this nociceptive transduction of heat (Mohammadi et al., 2013). This preliminary work establishes C. elegans as a quantitative model for thermal pain transduction, where the worm’s level of pain is statistically inferred by reading the “body language” of its nociceptive response, which allows us to objectively determine changes in pain transduction due to perturbations of genes, neurons, or experience. Our future projects follows up on this previous work by applying a systems-level, multi-disciplinary approach and implementing techniques from the areas of biophysics, genetics, and neuroscience. Currently we have three major projects that fall under this NSERC application toward the development of C. elegans as a model organism for nociceptive/pain transduction. The first is to screen C. elegans with analgesics using our laser pulse assay for pain quantification in order to understand how these analgesics modify behavior at the molecular level. The second is to investigate a receptor with unknown function that is involved in the pain response at the midbody of the worm. The third project involves the development of PVD, a neuron with highly branched processes, as a model neuron to study the biophysics of how a single neuron processes spatial sensory information.