Mechanical Stretch Inhibition Sensitizes Proprioceptors to Compressive Stresses

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