Soma 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
Question: Which properties of a neuron pair predict a functional connection (q < 0.05) in the optogenetic signal propagation atlas of Randi et al. (2023)? We compared soma distance with wiring from 10 electron microscopy (EM) connectomes. Data: 23,902 measured wild-type pairs, single-stimulation traces from 110 recordings, and ROI positions and red-channel signals from the DANDI release. Results: 26.9% of pairs with somata less than 5 um apart had q < 0.05. Only 2.1% of pairs 20 um or more apart had q < 0.05. Pairs with no synapse and no gap junction in any of the 10 connectomes gave 20.1% and 1.8%. In logistic models with neuron fixed effects, soma distance reduced the deviance by 498 and all wiring terms by 193. With distance in the model, chemical synapse terms did not predict detection. Near detections were 1.4% inhibitory; far detections were 28.3% inhibitory. The distance pattern also occurred in unc-31 mutants. For a fixed neuron pair, the response probability fell by 0.142 per doubling of in-plane image distance in that recording (95% CI 0.122 to 0.162). Distance along the optical axis had no clear effect (-0.007, CI -0.016 to 0.001). Spontaneous co-fluctuation of the same pairs fell equally with in-plane and axial distance, in the green and in the red channel. The evoked coupling did not change with relative brightness, as leaked fluorescence would require. Left-right homolog pairs, which are separated along the optical axis, also responded less at larger in-plane and axial distances. Conclusion: Near detections in this atlas follow recording geometry, not anatomy. Off-target activation by the two-photon spot (3.1 um wide, longer along the optical axis) agrees with these results. The recorded spot position did not improve the prediction for pairs without wiring, so this cause is not confirmed. Limitations: atlas positions and EM maps come from other animals; image units come from a fit; the analysis is exploratory. Structure-function tests with this atlas need a distance control.
C. elegans · signal propagation atlas · connectome · optogenetics · two-photon stimulation · off-target activation · soma distance · functional connectivity · structure-function · whole-brain calcium imaging · gap junctions · NeuroPAL · unc-31
References
11- usesdoi:10.1038/s41586-023-06683-4
Source of the signal propagation atlas (q values, responses, observation counts) that we analyse.
- usesdoi:10.17605/OSF.IO/E2SYT
OSF export of per-stimulation traces used for the event-level and coupling-gain tests.
- usesdoi:10.48324/dandi.001075/0.240930.1859
NWB files with per-recording ROI centroids, 2p target pixels and the red channel used for the within-pair geometry tests.
- usesdoi:10.1038/s41586-021-03778-8
Eight developmental connectomes, contact areas and connection classes used as wiring terms.
- usesdoi:10.1098/rstb.1986.0056
N2U and JSH brain connectomes used as wiring terms.
- usesdoi:10.1186/s12859-022-04738-3
NeuroPAL soma position atlas used for the primary distance measure.
- usesdoi:10.1371/journal.pcbi.1007974
Predicted synapse signs are included in the derived pair table.
- doi:10.1093/genetics/iyae077
Describes the TWISP strain and the optical setup of the atlas.
- supportsFive image position terms removed a 0.37% wiring gain in a fixed test of 1,225 C. elegans stimuli sci:sha256:696624f718fdadc24ed3ca7236e3cda00b94be6a43a6845907ed614523df82d2
That study found that image position terms remove a wiring gain but could not separate neural from optical effects; our within-pair geometry tests address that question and agree that position dominates.
- supportsAssuming independent animals and stable means, a cubic soma distance control reduced the estimated wiring overlap by 83% in 99 C. elegans worms sci:sha256:b79bb1d12567da2a4517745418d690f33a702bab98c5bf2adf177415a5f002a6
That study found that a soma distance control removes most of a wiring component; we show that soma distance predicts detection more than wiring does.
- supportsStable chemical connections across eight C. elegans connectomes did not propagate optogenetic signals more often than variable connections at matched adult synapse count sci:sha256:5cbb4c1917dff79c9e9f17c6ff6ae5d0ba556de73d1a96c2f13df319c7fef4d0
That study found that stable chemical connections do not propagate signals more often; we find no chemical synapse effect after a distance control.
Cited by
4 publicationsPublic catalog entries on Sciscape.
- Green and green/red rules gave opposite response signs in 18.2% of 48,300 measurements from 103 C. elegans recordings
This prior study measured distance and optical-axis effects in the assay. The present readout comparison does not identify an optical cause.
- usesChemical inputs from cells near the light spot gave no clear link to positive calcium responses in a fixed test of 2,417 distant neuron pairs in immobilized C. elegans
We reuse its verified event summaries, anatomical pair tables, cell-label checks and image-scale estimates. It also motivates the possible relay route.
- usesAt 5 micrometres, relay scores gave no clear gain in a fixed ridge test of calcium responses from 101 C. elegans worms
We use its verified soma atlas facts and recording image geometry for prediction controls.
- usesWith a fixed optical kernel, nearby cell wiring scores raised response magnitude test error by 0.16% in 93 C. elegans recordings
Its within-pair image geometry result motivates the question. We use its fitted pixel and scan-plane scales. We test a consequence of possible nearby source recruitment; we do not claim that its proposed optical cause was proved.