Modulation of touch sensitivity in Caenorhabditis elegans

Sensory perception adapts to diverse environment. Although studies in the last few decades have started to address the question of how sensory systems transduce signals, how these systems cross-modulated is largely unknown. In this thesis, I study mechanosensation in the C. elegans touch receptor neurons (TRNs) to understand how sensory systems are modulated and adapt to the environment. I find that the touch sensitivity in the TRNs is modulated by both mechanical and non-mechanical factors. The mechanical factors are transduced directly by a secondary mechanosensory system in the TRNs, and the non-mechanical factors are detected by other neurons and relayed to the TRNs by neuropeptides. Both pathways converge through a common mechanism to regulate the surface expression of the MEC-4 mechanotransduction channels, which are needed for sensing touch. I then explore the consequences of modulation, and show that modulation by mechanical and non-mechanical factors adjusts the balance between the sensitivity to strong mechanical stimuli that predict dangers and sensitivity to weak stimuli that are usually not associated with danger. Such a balance maintains sensitivity to biologically-relevant mechanical stimuli while reducing unnecessary responses to weak stimuli, thus increasing the ability to survive under different conditions. I used neuronal-enhanced RNAi and mosaic analysis to discover two convergent signaling pathways, the integrin/focal adhesion signaling and insulin signaling, that modulate anterior touch sensitivity. Additional genes and pathways are also needed for optimal touch sensitivity in the TRNs, including the RAS/MAPK pathway, Rho-GTPases, cytoskeleton genes, and 43 other genes that cause lethality when mutated. The integrins/focal adhesion proteins act cell-autonomously in the TRNs to detect the mechanical environment. The focal adhesion proteins modulate force sensitivity and subsequent calcium signaling, and they are needed for long-term sensitization of touch sensitivity in response to sustained background vibration. Such sensitization maintains normal touch sensitivity under background vibration by partially counteracting the effect of habituation. This sensitization does not require the MEC-4/MEC-10 transduction channel, suggesting that the integrins may act as secondary force sensors. Insulin signaling, however, responds to non-mechanical signals that reduce touch sensitivity by decreasing the expression of insulin-like neuromodulators, including INS-10 and INS-22. The reduced touch sensitivity facilitates the completion of other tasks such as chemotaxis under background mechanical stimuli, thus increasing the chance of survival by escaping stressful conditions. Both insulin signaling and integrin signaling converge on AKT-1 and DAF-16, which modulate touch sensitivity by regulating the transcription of mfb-1, an E3 ubiquitin ligase expressed in the TRNs. MFB-1 regulates the amount of MEC-4 channel on the plasma membrane, thus modulating touch sensitivity. Together, these results describe an integrated pathway that transduces both mechanical and non-mechanical signals to modulate touch sensitivity through a common mechanism. These modulation mechanisms maintain optimal sensitivity to mechanical stimuli while avoiding unnecessary responses