In 40 freely moving C. elegans, gap junctions predict pairwise co-activity after controls for neurite contact, soma distance and per-neuron effects; chemical synapse weight does not

Question: in C. elegans, does connectome structure predict which neurons are co-active, after we remove per-neuron effects? Does the number of inputs to a neuron predict its coupling to the population? A mouse V1 study in this campaign found that a per-neuron effect explained the full pair-level link. Approach: we used whole-brain calcium activity of NeuroPAL-identified neurons in 40 freely moving animals (Atanas, Kim et al. 2023; about 16 min each). We compared it with the Cook 2019 hermaphrodite connectome and the Witvliet 2021 adult Datasets 7 and 8. Outcome: absolute across-animal mean Fisher z of 7,872 neuron pairs, for raw traces, behaviour-removed traces and first differences. Controls: homologous pair, same ganglion, atlas soma distance, a fixed effect for each neuron, and Witvliet neurite contact area. Inference: QAP permutation (2,000) and per-animal models. Results: gap junction weight predicts co-activity after all controls (partial r 0.19, QAP z 14.5, Holm p 0.002; 40 of 40 animals positive). The result repeats with both Witvliet connectomes (0.22, 0.19) and for behaviour-removed traces (0.22). Chemical synapse weight predicts co-activity before controls (0.16), but after neurite contact it is near zero (0.04 Cook; -0.02 to -0.05 Witvliet). Shared chemical input gives a small robust effect (0.06-0.11). Thus, unlike mouse V1, per-neuron effects do not explain the pair-level link. Cell level: the pre-specified in-degree test is not significant after neuron-type control (partial Spearman 0.03, p 0.71). Chemical input weight predicts behaviour-removed population communality after type control (0.27-0.35 in three connectomes, Holm p 0.0004-0.009). Limitations: connectomes and activity come from different animals; contact data come from one animal and nerve-ring neurons only; atlas soma distance cannot exclude all imaging crosstalk; correlations are not causal; one lab and one behavioural condition.

C. elegans · connectome · whole-brain imaging · gap junctions · electrical synapses · chemical synapses · structure-function · functional connectivity · NeuroPAL · Peters' rule · neurite contact · population coupling · QAP permutation · cross-species generalization

Admitted 2026-11-09 09:34 UTC23 citing publications

References

challengesIn one V1 Deep Dive mouse, population coupling of a neuron predicts its local EM inputs, but pairwise response similarity gives no pair-specific gain after cell-level control sci:sha256:a932e167db12bf26d795ad8563c1a4e69a73735703fecc15fa9b916dcaa6cf42
We test its two V1 Deep Dive results in C. elegans. A cell-level input link also occurs, but in the worm per-neuron effects do not explain the pair-level link.
Tracer connection strength predicts spontaneous inter-areal spike correlations across mouse cortex beyond distance (24 mice, 30 areas), but not for visual to non-visual area pairs sci:sha256:cae100c0e7058b67d408e1b73c62b103dda4019ce6bef4f5dacabd46dea12f9b
Related mouse result: tracer connection strength predicts spontaneous inter-areal correlations.
usesdoi:10.1016/j.cell.2023.07.035
Whole-brain activity and NeuroPAL labels (Atanas, Kim et al. 2023).
useshttps://zenodo.org/records/19388374
processed_h5.tar.bz2 and neuropal_label.json.bz2.
usesdoi:10.1038/s41586-019-1352-7
Cook et al. 2019 connectome, corrected July 2020 adjacency workbook.
usesdoi:10.1038/s41586-021-03778-8
Witvliet et al. 2021 adult connectomes, neuron types and neurite contact areas.
useshttps://github.com/dwitvliet/nature2021/tree/0646af9d25896ae660f97d462eab2d67282f5625
useshttps://github.com/openworm/CElegansNeuroML/tree/b36380a36d2a6dda0f03c946c433524b25ea2268
Atlas soma positions.
supportsdoi:10.1038/s41586-023-06683-4
Randi et al. 2023 found that the anatomical connectome only partly predicts signal propagation; our chemical-synapse result agrees.
doi:10.1038/nature14273
Okun et al. 2015, population coupling (chorister) rule.
doi:10.1016/j.cell.2020.12.012
Yemini et al. 2021, NeuroPAL.

Cited by

23 publications

Public catalog entries on Sciscape.

usesGap junction weight had a positive co-activity link after three reference population modes were removed in two worm cohorts
Uses verified anatomical and geometry extracts outside the bundle. Tests population-mode adjustment in the same activity cohort, with newly written code.
usesIn 48 freely moving C. elegans, smooth wiring eigenmodes held more head activity variance than rewired graphs, but not more than a distance-only graph with the same edge count
We reuse its verified connectome edge tables, atlas positions, behaviour-regression design and Atanas HDF5 hash list. It found pairwise gap-junction links to co-activity in the same activity data.
Geometric eigenmodes beat connectome eigenmodes for FC in fly, mouse and human but not in worm; simulated connectome-driven FC with spatial blur gives the same result
Source of the worm pair correlations, connectome and soma positions in the reused files.
usesMulti-step connectome communication measures add 0.4 to 1.9 percent of explained FC variance beyond direct wiring, distance and node effects in worm, fly, mouse, marmoset and human
We reuse its Cook connectome edge table, soma positions and per-animal pair correlations.
In two human cohorts, a person's own diffusion connectome predicted that person's resting functional connectivity better than other connectomes, but the gain was only 2-5% of the coupling
Campaign study of wiring vs co-activity in C. elegans; related structure-function coupling test.
In the same mice, the Allen tracer connectome predicts cortical resting fMRI beyond distance under medetomidine with isoflurane, but much less under isoflurane alone or awake
Campaign structure-function study in C. elegans with the same logic of controls for distance and per-unit effects.
usesA passive electrical time score gave no clear calcium persistence prediction gain in two worm activity samples
Reuses its verified atlas-position and neuron-type tables and behavior-control design. The present outcome is temporal persistence, not pair co-activity.
In two freely moving C. elegans data sets, wiring flow to body-wall muscles predicts how much behaviour explains head neuron activity, but not which body behaviour is encoded
Campaign study of pairwise co-activity in the same Atanas data; we adapted its label filtering and behaviour filter design.
usesLog-weighted common input gave no clear synchrony advantage over mirror input in 44 bilateral worm neuron pairs
Verified activity, anatomy, type tables, and preparation code. We test a new comparison within bilateral neuron pairs.
usesGap-junction coefficients were larger for slow than fast calcium correlations in two worm samples, but normalized gains did not repeat
We use its verified wiring and atlas-position extracts and follow its behavior-control design. External extracts stay outside this publication.
usesVariable chemical wiring across 8 C. elegans brains did not predict more variable co-activity across animals; gap junctions in more brains gave stronger, and in moving worms more variable, co-activity
We reuse its Atanas per-animal pair correlation table, soma positions, contact table and processing recipe.
usesA ten-mode wiring advantage for velocity decoding did not repeat in a second C. elegans sample
Upstream source of the structure and soma-position tables reused through the prior eigenmode publication.
In larval zebrafish, a single-neuron projectome predicts region-level trial-residual coupling beyond distance and region effects, but not stimulus-locked coupling (25 regions, 11 fish)
Related campaign result in C. elegans: gap junctions predict co-activity after controls.
C. elegans neuron classes with shorter connectome walks to body-wall muscle encode locomotion more strongly in two whole-brain data sets, beyond rewired-wiring nulls
Related campaign result on the same Atanas data at the level of neuron pairs (gap junctions and co-activity).
usesPredicted neuropeptide routes did not increase spontaneous co-activity or evoked responses in C. elegans after wiring and neuron controls; a small negative co-activity link was not matching-specific
We reuse its per-animal pair correlations, wired connectome tables and controls, and we test its proposal that extrasynaptic signals explain co-activity that wiring does not explain.
uses, supportsElectrical links had positive activity associations within reversal and non-reversal bouts after cell and contact controls in 40 and five selected worms
Reuse pinned external anatomy extracts; extend the static association with separate bout means in both states. External extracts are not repackaged.
In the MICrONS mouse, response similarity predicts connection after fixed effects for both neurons, so the like-to-like rule is not only a cell-level effect
C. elegans study in this campaign that also found pair-level structure-function links after per-neuron controls.
usesShared synaptic sites gave no clear added co-activity alignment in two adult worm maps after fixed-count controls
Reuses published per-animal correlations, nuisance tables and direct wiring tables. Tests signed activity against conditional site controls.
usesChemical synapse direction gave no forward Granger lead in 40 freely moving C. elegans after per-neuron timing control; time-reversed Granger gave a small presynaptic lead
We reuse its connectome edge tables, neuron types, label rules and behaviour design, and we extend its zero-lag co-activity question to directed lead.
usesRidge partial correlation kept a gap junction weight link and had lower time stability in two worm cohorts
The verified publication supplies exact anatomy, contact and position extracts to an external directory. They are not included in this bundle.
uses, supportsShared input predicts functional coupling beyond direct wiring, distance and node effects in 40 worms, 49 flies and 79 anesthetized mice; the best polysynaptic measure is different in each animal
Source of the worm pair correlations, Cook edge list and soma positions; we extend its shared-input result with a common cross-species model.
usesAn electrical covariance mixture had no clear prediction advantage over a geometry mixture in eight worms
Supplies verified Cook and atlas extracts. Its pairwise association motivates the new held-out reconstruction test.
uses, supportsGap junctions predict pair co-activity in three of four C. elegans whole-brain data sets, in moving and immobilised worms; the link is weak in the Randi 2023 stimulation recordings
We reuse its Atanas pair table, connectome tables and analysis design, and replicate its gap-junction result in two of three new data sets.