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Postsynaptic natural-movie reliability gave 4% higher connection odds per SD in two mouse visual cortex EM datasets; presynaptic and assortative reliability effects were not consistent

Question: is the trial-to-trial reliability of natural-movie responses related to local synaptic connectivity in mouse visual cortex? We tested three hypotheses: reliable neurons receive more connections (H1), make more connections (H2), or connect preferentially to other reliable neurons (H3). Data: MICrONS functional connectomics tables (Ding et al. 2025, v1; 275,681 axon-dendrite proximity pairs, 144 presynaptic and 10,591 postsynaptic neurons, 7,529 connections) and the Allen V1 Deep Dive mouse (EM release 1196; 99,215 pairs among coregistered cells, 193 presynaptic and 515 postsynaptic cells, 1,447 connections). Reliability is the CCmax correlation ceiling from movie repeats, z-scored within imaging strata. Method: logistic regression with presynaptic (H1, H3) or postsynaptic (H2) fixed effects and geometry splines, two-way cluster-robust intervals, cell-level score-permutation tests, and inverse-variance pooling. Results: postsynaptic reliability increased connection odds by 4.2% per SD in MICrONS (95% CI 1.2-7.2%, permutation p = 0.0004) and by 5.2% in V1DD (CI -2.4 to 13.3%, p = 0.21). The pooled odds ratio was 1.043 (1.016-1.072) without heterogeneity. It stayed after control for pair signal correlation (1.032, 1.005-1.060) and for postsynaptic signal coupling (1.038, 1.010-1.066). The effect is about one third of the like-to-like signal-correlation effect. Presynaptic reliability gave no clear effect in either mouse (permutation p = 0.46 and 0.25). The pre x post interaction had opposite signs in the two mice (1.038 and 0.955; heterogeneity p = 0.008), so the data do not support a reliable-neuron rich club. Limitations: observational data with one mouse per dataset; V1DD has soma-distance controls but no proximity measure; the MICrONS presynaptic sample is small and highly reliable; the final model list was set after one exploratory MICrONS estimate; no multiplicity correction.

MICrONS · V1 Deep Dive · Allen Institute · functional connectomics · response reliability · CCmax · synaptic connectivity · in-degree · like-to-like · mouse visual cortex · structure-function · null result

Admitted 7 citing publications

References

11
  1. usesdoi:10.1038/s41586-025-08840-3

    Source of the MICrONS functional connectomics node and edge tables (release v1), including CCmax and axon-dendrite proximity pairs.

  2. useshttps://bossdb-open-data.s3.amazonaws.com/iarpa_microns/minnie/functional_data/functional_connectomics/node_and_edge_properties/v1/

    Download location of node_data_v1.pkl and edge_data_v1.pkl.

  3. useshttps://aind-open-data.s3.amazonaws.com/v1dd-analysis-1196-1_2025-08-14_16-38-00/

    Allen V1 Deep Dive EM release 1196: synapses, somata and proofread lists.

  4. useshttps://aind-open-data.s3.amazonaws.com/409828_V1DD_coreg_functional_correlation_2026-08-20_18-43-32/

    V1DD two-photon to EM coregistration table (coregistration_1196.feather).

  5. useshttps://aind-open-data.s3.amazonaws.com/409828_2018-12-13_15-10-05_filtered_2026-04-09_05-57-20/

    One of the three coregistered V1DD two-photon sessions (c1v3); c1v5 and c2v5 are listed in the README provenance.

  6. usesdoi:10.3389/fncom.2016.00010

    Schoppe et al. 2016: normalized correlation ceiling (CCmax) estimator.

  7. usesdoi:10.1198/jbes.2010.07136

    Cameron, Gelbach and Miller 2011: multi-way cluster-robust inference.

  8. 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 sci:sha256:eab8ce57aa9d50d12c54327bd737b6d67304e2e8291015223a987a93d69661c4

    Campaign study of like-to-like wiring and postsynaptic signal coupling in the same MICrONS pairs; motivated our coupling control.

  9. 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 sci:sha256:c59a7cc9c394931da48264dbdd64f4dd2ef21ea50f820313c35558be9be14d07

    Campaign study of like-to-like wiring with two-way fixed effects in MICrONS.

  10. In 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

    Campaign study of V1DD population coupling and EM inputs in the same coregistered cells.

  11. doi:10.1038/nature14273

    Okun et al. 2015: population coupling and synaptic input, a related cell-level property.

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