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Cell-level signal coupling does not explain like-to-like wiring in the MICrONS mouse: connection odds increase 8-14% per SD of response similarity in 295,371 cotravel pairs

Question: in the MICrONS mouse visual cortex, do connected neurons have more similar responses because of a property of the pair, or because of a property of one cell? A campaign study of the V1 Deep Dive mouse found that cell-level control removed the pair-level effect. Approach: we used the public tables of Ding et al. (2025): 148 presynaptic neurons with proofread axons, 11,035 postsynaptic neurons, 295,371 axon-dendrite cotravel pairs and 8,128 connected pairs. We wrote the analysis plan before we computed results. Pair level: after control for cotravel length, the odds ratio (OR) of connection per SD of in silico signal correlation was 1.16 (95% CI 1.13-1.19). With control for postsynaptic coupling and mean similarity, the OR was 1.14 (1.11-1.17). Conditional on the postsynaptic cell, the OR was 1.08 (1.05-1.11), or 1.12 with presynaptic controls. A linear model with presynaptic and postsynaptic fixed effects gave +0.39 percentage points per SD (base rate 2.75%). In vivo signal correlation and readout similarity gave the same result. Orientation similarity gave no clear effect. Layer/area pair types and receptive-field distance did not remove the effect (OR 1.16-1.19). Cell level: postsynaptic signal coupling predicted in-degree beyond cotravel (rate ratio 1.05 per SD, permutation p = 0.003), in V1 and L5 but not in L2/3 or higher visual areas. Presynaptic coupling did not increase out-degree. In subsamples of V1DD size (785 connections), the in vivo CI excluded 1 in 74% of draws, and 2.9% of draws gave OR <= 1.01 (the V1DD estimate). Limitations: one animal per data set; different similarity estimates and candidate pairs in the two data sets; no spontaneous or noise coupling in the release; 112 of 148 presynaptic cells are in RL and AL; some axons are proofread only for projections; subset and sensitivity analyses are exploratory.

functional connectomics · MICrONS · like-to-like connectivity · population coupling · signal correlation · electron microscopy · two-photon imaging · mouse visual cortex · digital twin · structure-function · cross-animal replication · conditional logistic regression

Admitted 7 citing publications

References

6
  1. supports, 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

    Tests its V1DD findings in a second mouse. A small postsynaptic coupling effect on in-degree agrees with its natural-movie estimate. The pair-level like-to-like effect stays after cell-level control here, which does not agree with its pair-level null result.

  2. uses, supportsdoi:10.1038/s41586-025-08840-3

    Source of the node and edge tables. We replicate its like-to-like result and show that cell-level coupling does not explain it.

  3. usesdoi:10.1038/s41586-025-08790-w

    MICrONS data set (mouse 17797).

  4. useshttps://bossdb-open-data.s3.amazonaws.com/iarpa_microns/minnie/functional_data/functional_connectomics/node_and_edge_properties/v1/edge_data_v1.pkl
  5. useshttps://bossdb-open-data.s3.amazonaws.com/iarpa_microns/minnie/functional_data/functional_connectomics/node_and_edge_properties/v1/node_data_v1.pkl
  6. doi:10.1038/nature14273

    Okun et al. 2015: population coupling and local synaptic input (chorister hypothesis).

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