PT - JOURNAL ARTICLE AU - Magaram, Uri AU - Weiss, Connor AU - Vasan, Aditya AU - Reddy, Kirthi C. AU - Friend, James AU - Chalasani, Sreekanth H. TI - Two parallel pathways are required for ultrasound-evoked behavioral changes in <em>Caenorhabditis elegans</em> AID - 10.1101/2021.10.29.466533 DP - 2021 Jan 01 TA - bioRxiv PG - 2021.10.29.466533 4099 - http://biorxiv.org/content/early/2021/11/02/2021.10.29.466533.short 4100 - http://biorxiv.org/content/early/2021/11/02/2021.10.29.466533.full AB - Ultrasound has been shown to affect the function of both neurons and non-neuronal cells. However, the underlying molecular machinery has been poorly understood. Here, we show that at least two mechanosensitive proteins act in parallel to generate C. elegans behavioral responses to ultrasound stimuli. We first show that these animals generate reversals in response to a single 10 msec pulse from a 2.25 MHz ultrasound transducer. Next, we show that the pore-forming subunit of the mechanosensitive channel TRP-4, and a DEG/ENaC/ASIC ion channel MEC-4, are both required for this ultrasound-evoked reversal response. Further, the trp-4 mec-4 double mutant shows a stronger behavioral deficit compared to either single mutant. Finally, overexpressing TRP-4 in specific chemosensory neurons can rescue the ultrasound-triggered behavioral deficit in the mec-4 null mutant, suggesting that these two pathways act in parallel. Together, we demonstrate that multiple mechanosensitive proteins likely cooperate to transform ultrasound stimuli into behavioral changes.Competing Interest StatementThe authors have declared no competing interest.