A proprioceptive feedback circuit drives C. elegans locomotor adaptation through dopamine signaling

An animal adapts its motor behavior to navigate through the external environment. This adaptation depends on proprioception, which provides feedback on an animal’s body postures. How proprioception mechanisms interact with motor circuits and contribute to locomotor adaptation remains unclear. Here we describe and characterize proprioception-mediated homeostatic control of undulatory movement in the roundworm Caenorhabditis elegans. We found the worm responds to optogenetically or mechanically induced decreases in mid-body bending amplitude by increasing its anterior amplitude. Conversely, it responds to increased mid-body amplitude by decreasing the anterior amplitude. Using genetics, microfluidic and optogenetic perturbation response analyses, and optical neurophysiology, we elucidated the neural circuit underlying this compensatory postural response. The dopaminergic PDE neurons sense mid-body bending and signal to AVK interneurons via the D2-like dopamine receptor DOP-3. The FMRFamide-like neuropeptide FLP-1, released by AVK, regulates SMB head motor neurons to modulate anterior bending. We propose that this homeostatic behavioral control optimizes the efficiency of locomotion. Our findings demonstrate a mechanism in which proprioception works with dopamine and neuropeptide signaling to mediate motor control, a motif that may be conserved in other animals.

Methods
(A) Folder 'Biomechanical experiments' contains original videos of locomotion of C. elegans in viscous fluids.  Worms were placed in chambers filled with dextran solutions.  Worm locomotion was collected by CCD camera mounted on a microscope.  Data were processed by customized behavioral analyzing code provided along.
The name of the each subfolder is in the format "XXXX-XX-XX_XX_XXpct", denoting the time, strain name, and viscosity of the medium. In each subfolder: 
(1) AVI files represent video recordings in both dark-field mode and binary mode. 
(2) MAT and TXT files represent intermediate data derived from the post-acquisition analysis of the video recordings; the post-acquisition analysis code is available from the referred article (link of the article is provided in this repository). Within the MAT and TXT file, the meaning of each variable is described in the data repository associated with the referred article.

(B) Folder 'Compensatory experiments' (part I to VI) contains original videos (in AVI format) of free and constrained locomotion of C. elegans in NGM buffer.  Worms were placed in microfluidic devices with narrow channels for constraining specific regions of worms.  Worm locomotion was collected by CMOS camera.  Data were processed by customized analyzing code provided along.
The name of the each subfolder is in the format "XXXX_XXXX_XXXX-XX-XX", denoting the strain name, channel width, and time of experiments.

(C) Folder 'GCAMP experiments' (part I to IV) contains original image sequences (in TIF format) of worms with specific neurons tagged with GCaMP or GFP.  Worms (strains include BZ555 and SWF331 as indicated by the subfolder name) were prepared either onto agarose pads capped with a cover glass, or in a viscous fluid (45 per cent dextran solution), or in a microfluidic chamber patterned with sinusoidal channels (preparation method is indicated by the subfolder name: "agar freemove", "fluid freemove", and "microfluidic sinusoidal").  Worms were able to freely move around or were paralyzed due to genetic mutations. 

(D) Folder 'Validation of fluo expr': This folder contains images for validating successful ablations of specific neurons labelled with fluorescence.  All data were collected on a fluorescence microscope.  Images were processed by using ImageJ software and customized phython scripts provided along.The name of the each subfolder indicate the conditions of experiments, including the time, strain name, and/or the neurons being ablated.

(E) Folder 'Optogenetic experiments' contains original videos of transgenic worms with specific cells inhibited or stimulated by a laser targeting system.  Worms were placed in chambers filled with dextran solutions.  Worm locomotion was recorded by CCD camera mounted on a microscope.  Data were processed by customized C++ scripts developed by Dr Fouad et al (https://doi.org/10.7554/eLife.29913). 
The name of the each subfolder indicate the conditions of experiments, including the time, strain name, and viscosity of the medium, location of illumination, duration of light pulse, and the use of polarizers. In each subfolder: 
(1) AVI files represent video recordings in both dark-field mode and binary mode. 
(2) MAT and TXT files represent intermediate data derived from the post-acquisition analysis of the video recordings; the post-acquisition analysis code is available from the referred article (link of the article is provided in this repository). Within the MAT and TXT file, the meaning of each variable is described in the data repository associated with the referred article.