In 40 moving C. elegans, behaviour-locked activity held 56% of reliable pair-specific co-activity and wiring at most 5% of the rest; in 22 zebrafish larvae swim and flash terms held 24-36%
Question: earlier campaign work found that pair-specific functional connectivity (FC, after node effects and distance) is very reliable, that wiring explains only 3-11% of it, and that rank-3 node factors hold most of it. What are these factors? Method: in each animal we fitted every neuron or region with a cross-validated ridge model of lagged behaviour (worm: velocity, reversal, head angle, angular velocity, pumping, curvature, body shape; zebrafish: swim and dark-flash terms). This splits each pair covariance into behaviour-explained, residual and cross parts. Split-half covariances across animals measured the share of the reliable pair-specific map in each part; a control used time-shifted behaviour. Three-part splits tested tuning maps and node factors from other animals. Data: 40 off-food worms (Atanas 2023; 119 neurons), 8 on-food worms (Dag 2023), 22 larval zebrafish (Legare 2025; 65 regions). Results: in worms, 56% (95% CI 52-60%) of the reliable pair-specific covariance was behaviour-locked (shifted control 2%) and 27% survived as reliable residual covariance; on food, 72% (58-85%). In zebrafish, 36% (26-46%) with flashes and 24% (17-31%) in spontaneous activity. A map made only from other animals' tuning coefficients removed 55% of the reliable worm map, equal to a rank-1 factor. The worm factors were the forward-reversal axis (r = 0.72 with reversal tuning), a slow session drift (r = 0.61 with time) and pumping (r = 0.38). Removing behaviour did not unmask wiring: wiring explained 2.5% before and 2.8-5.4% after (time-shifted controls 3.0-3.1%). In the residual, a type-by-transmitter block model explained 13.5% (null 2.0%; on food 12.3%). Limitations: behaviour-locked is not behaviour-caused; linear model with measured variables only; the drift factor can be state or trace processing; connectome and activity from different animals; identity analysis and variants were post hoc; no fly time series.
References
18- usesIn 40 worms, 50 flies and 22 larval zebrafish, wiring explained 2-24% of the reliable pair-specific coupling after node and distance controls; the link was pair-specific, and only swimming changed it
- usesWiring explained 5% (worm), 11% (zebrafish) and 24% (fly) of reliable pair-specific FC; much fly and mouse wiring signal was a smooth spatial field; of three behaviours only swimming raised the share
- usesIn 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
- Shared 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
- In fly, mouse and human data, surrogate wiring with matched node strengths and distances reproduced 48-100% of the FC gain of indirect-path measures; a large specific gain stayed only in sedated mouse
- 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
- In 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
- FlyWire wiring predicts neuropil calcium correlations beyond distance in 50 flies; walking and rest coupling agree after global-signal removal; transmitter-matched wiring adds no gain
- Single-neuron axon co-innervation predicted spike correlations between 30 mouse cortical areas, but real collateral patterns did not predict better than source-matched shuffles at 100 ms
- 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)
- NSM serotonergic state did not change wiring coupling of co-activity in 40 off-food C. elegans; an on-food decrease in 8 worms matched a drop in activity variance
- In 20 larval zebrafish, mapZebrain wiring predicts region coupling beyond distance and region effects; near swim bouts all spatial structure of coupling increases
- doi:10.1016/j.cell.2023.07.035
- doi:10.1016/j.cell.2023.04.023
- doi:10.1126/sciadv.adv7576
- doi:10.1038/s41586-019-1352-7
- doi:10.7554/eLife.95402
- doi:10.1038/s41586-021-03778-8