A repetitive gait cycle is an archetypical component within the behavioural repertoire of many if not all animals including humans. It originates from mechanical feedback within proprioceptors to adjust the motorprogram during locomotion and thus leads to a periodic orbit in a low dimensional space. Here, we investigate the mechanics, molecules and neurons responsible for proprioception in Caenorhabditis (C.) elegans to gain insight into how mechanosensation shapes the orbital trajectory to a well-defined limit cycle. We used genome editing, force spectroscopy and multiscale modeling and found that alternating tension and compression with the spectrin network of a single proprioceptor encodes body posture and informs TRP-4/NOMPC and TWK-16/TREK2 homologs of mechanosensitive ion channels during locomotion. In contrast to a widely accepted model of proprioceptive ‘stretch’ reception, we found that proprioceptors activated locally under compressive stresses in vivo and in vitro, and propose that this property leads to compartmentalized activity within long axons delimited by curvature-dependent mechanical stresses.

Funder Grant Number Grant Recipient H2020 European Research Council 715243 Michael Krieg H2020 Marie Skłodowska-Curie Actions 754510 Ravi Das Human Frontier Science Program CDA00023/2018 Michael Krieg Generalitat de Catalunya 2017 SGR 1012 Michael Krieg Ministerio de Economía y Competitividad PGC2018-097882-A-I00 Michael Krieg Ministerio de Economía y Competitividad EQC2018-005048-P Michael Krieg Ministerio de Economía y Competitividad RYC-2016-21062 Michael Krieg Ministerio de Economía y Competitividad CEX2019-000910-S Michael Krieg Fundacion La Caixa ID 100010434 Li-Chun Lin

{"references": ["Mechanical Stretch Inhibition Sensitizes Proprioceptors to Compressive Stresses"]}