Stable chemical connections across eight C. elegans connectomes did not propagate optogenetic signals more often than variable connections at matched adult synapse count
Question: Witvliet et al. (2021) classified the chemical connections in eight isogenic C. elegans brains as stable or variable between animals. Do stable connections carry measurable signal propagation more often than variable connections of the same size? Approach: We joined the Witvliet classes and synapse counts with the Randi et al. (2023) optogenetic signal propagation atlas. We used 15,384 measured ordered head neuron pairs (stimulated j, responding i). We wrote the analysis plan before we tabulated outcomes. The primary test was a Mantel-Haenszel odds ratio, stable vs variable connection j->i, for detection (q < 0.05) across six adult synapse count strata. We added logistic models with cluster bootstraps, neuron fixed effects, and 13 sensitivity analyses. Results: Stable connections did not show propagation more often than variable connections. The primary odds ratio was 0.46 (95% CI 0.21-1.00). All 15 analyses gave odds ratios below 1 (0.31-0.74). The direction variable > stable was not robust: without the 114 left/right homolog pairs the odds ratio was 0.55 (0.25-1.22). Detection rates were 5.6% (28/500) for stable connections, 8.0% (79/983) for variable connections, and 5.1% (700/13,654) for pairs with no j->i chemical synapse in any animal. Edges in both adult animals were not detected more often than edges in one adult (odds ratio 1.27, 0.60-2.70). Left/right homolog pairs (47%) and gap junctions (11%) predicted detection much better than chemical synapses (7%), and the synapse direction added nothing measurable. Of 138 stable connections with at least 8 adult synapses, 84 (61%) met the atlas criterion for functional non-connection (q_eq < 0.05). Conclusion: In this atlas, consistency of a chemical connection across animals did not identify the connections that carry measurable signal propagation. Main limitation: detection was rare (median 3 trials per pair), and the atlas measures somatic calcium in a fixed window, so inhibitory, slow, or compartmentalized effects can stay below detection. The data exclude a large advantage for stable connections but not a small one. EM and imaged animals are different individuals.
C. elegans · connectome · connectome variability · signal propagation atlas · functional connectivity · optogenetics · structure-function · chemical synapse · gap junction · Witvliet 2021 · Randi 2023 · pre-specified analysis
References
4- usesdoi:10.1038/s41586-021-03778-8
Source of the eight EM connectomes, the stable/variable/developmental connection classes, and the per-dataset synapse and gap junction counts (GitHub dwitvliet/nature2021, commit 0646af9).
- usesdoi:10.1038/s41586-023-06683-4
Source of the wild-type and unc-31 signal propagation atlas (q, q_eq, dF/F, trial counts) from the wormneuroatlas 0.0.7.3 package.
- doi:10.1038/nature11081
Shows compartmentalized calcium in RIA, one reason why the atlas can miss responses to strong synaptic input.
- supportsA synapse count rule selected the larger absolute calcium response in 140 of 310 C. elegans atlas pairs with at least five trials per direction sci:sha256:8415f4434c1d662db2900bdc7768e73baa29298f62a5ac491f42f08e0f9cca2a
Our finding that a chemical synapse i->j predicts detection as well as one j->i (7.1% vs 7.3%) agrees with its finding that chemical count direction did not pick the larger atlas response.
Cited by
16 publicationsPublic catalog entries on Sciscape.
- usesElectrical links found in two maps gave no clear extra calcium correlation term at fixed contact count in 21 C. elegans recordings
This prior study tested chemical link stability and two-adult agreement against optogenetic detection. We use its question as context and test electrical links against spontaneous calcium correlation.
- In a 30-second window, 315 of 668 selected C. elegans kernels with peaks before one second had most absolute area after one second
This earlier study tested wiring stability against response detection in the same atlas. Our outcome is fitted kernel peak time.
- supportsSoma distance predicted detected connections in the C. elegans signal propagation atlas more than EM wiring, and near responses followed in-plane image distance within neuron pairs
That study found that stable chemical connections do not propagate signals more often; we find no chemical synapse effect after a distance control.
- A fixed model gave a 0.000009 mean Brier gain from two-step electrical paths in 15,384 C. elegans atlas pairs
Prior SCI work compared direct chemical stability and gap junctions with signal detection. This study tests indirect electrical paths.
- Mirror synapse counts did not lower response detection error in 9,725 C. elegans atlas pairs under a fixed logistic model
This study tested developmental stability classes against response detection in the same functional export. It helped define the controls and source audit.
- supportsPharynx controls reduced the added prediction gain from indirect walks by 89% in a fixed C. elegans atlas test
Its direct chemical and gap-junction findings motivated the direct-link control. We ask a different question about indirect-walk prediction for excluded bilateral groups.
- A flag for two-edge chemical routes in an adult map increased Brier error in a fixed model of calcium response detection for 3,293 C. elegans atlas pairs
This is prior work on direct chemical connection stability and response detection in the same source atlas.
- In four C. elegans maps with two-way electrical links, route length had rank correlations of 0.03–0.10 with fitted mean kernel peak time
This earlier test studies stable wiring and response detection. The present study tests fitted kernel peak time.
- Count differences between two adult maps gave no clear gain in a ridge test of response spread across worms for 370 C. elegans neuron pairs
This prior study tested structural consistency for response detection. The current outcome is spread across named animals.
- Anatomy reduced ridge test error by 4.35% in wild type and increased it by 0.98% in unc-31 for 1,342 matched C. elegans atlas pairs
This related study tests chemical connection stability against response detection in the same functional export.
- Adding a term for paths in either adult worm raised test Brier error in a fixed model of 8,008 C. elegans atlas pairs
This prior analysis joins anatomical connection stability with the same response atlas. We test short-path provenance instead.
- Adding a count of paths within one map reduced Brier error by 0.000014 in a fixed test of 21,074 C. elegans pairs without recorded direct edges
Related test of chemical connection stability against response detection in the same atlas.
- Two adult C. elegans chemical maps gave no clear gain over two early maps in a fixed test of 8,265 calcium response directions
This study tested stable and variable chemical connection classes in the same functional atlas. We extend the question to age-specific graph prediction errors. We do not reuse its code or tables.
- Adult map labels raised Brier error after route count adjustment in 7,554 C. elegans atlas directions
This study provides prior results on direct chemical connection stability and functional detection.
- Mirror response labels gave 2.0 percent lower mean Brier error in a fixed test of 4,017 C. elegans atlas entries
This prior SCI study compared stable chemical wiring with signal detection in the same functional atlas.
- Terms for wiring direction raised Brier error in fixed WT and unc-31 models of 3,261 C. elegans atlas pairs
Prior analysis of connection stability and functional response detection motivates controls for count, electrical wiring and bilateral identity.