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bioRxiv · 10.1101/2021.12.08.471862

Escape Steering by Cholecystokinin Peptidergic Signaling

Chen, L.·Liu, Y.·Su, P.·Hung, W.·Li, H.·Wang, Y.·Yue, Z.·Ge, M.·Wu, Z.·Zhang, Y.·Fei, P.·Chen, L.-M.·Tao, L.·Mao, H.·Zhen, M.·Gao, S.
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Abstract

Escape is an evolutionarily conserved and essential avoidance response. Considered to be innate, most studies on escape responses focused on hard-wired circuits. We report here that peptidergic signaling is an integral and necessary component of the Caenorhabditis elegans escape circuit. Combining genetic screening, electrophysiology and calcium imaging, we reveal that a neuropeptide NLP-18 and its cholecystokinin receptor CKR-1 enable the escape circuit to execute a full omega ({Omega}) turn, the last motor step where the animal robustly steers away from its original trajectory. We demonstrate in vivo and in vitro that CKR-1 is a Gq protein coupled receptor for NLP-18. in vivo, NLP-18 is mainly secreted by the gustatory sensory neuron (ASI) to activate CKR-1 in the head motor neuron (SMD) and the turn-initiating interneuron (AIB). Removal of NLP-18, removal of CKR-1, or specific knockdown of CKR-1 in SMD or AIB neurons lead to shallower turns hence less robust escape steering. Consistently, elevation of head motor neuron (SMD)s Ca2+ transients during escape steering is attenuated upon the removal of NLP-18 or CKR-1. in vitro, synthetic NLP-18 directly evokes CKR-1-dependent currents in oocytes and CKR-1-dependent Ca2+ transients in SMD. Thus, cholecystokinin signaling modulates an escape circuit to generate robust escape steering.

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Chen, L., Liu, Y., Su, P., Hung, W., Li, H., Wang, Y., Yue, Z., Ge, M., Wu, Z., Zhang, Y., Fei, P., Chen, L.-M., Tao, L., Mao, H., Zhen, M., Gao, S.. 2021-12-09. Escape Steering by Cholecystokinin Peptidergic Signaling. https://doi.org/10.1101/2021.12.08.471862

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