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In the V1 Deep Dive mouse, connected excitatory neurons had only slightly more similar movie responses than nearby unconnected neurons; the same test gave a 2 to 7 times larger effect in MICrONS

Question: the MICrONS study (Ding et al. 2025) found that connected excitatory neurons in mouse visual cortex respond more similarly to natural movies than unconnected neurons with the same axon-dendrite proximity. Does this like-to-like rule have the same size in a second mouse? Approach: we used the Allen V1 Deep Dive (V1DD) dataset (EM materialization 1196 and two-photon imaging of the same tissue, CC BY 4.0). 553 neurons are manually coregistered; 193 have proofread axons; they make 1,441 connections onto coregistered neurons with function and proximity. Proximity came from synapse-site clouds: axon output sites within 10 um of the input sites of the target. We compared each connected pair with unconnected pairs of the same presynaptic cell, proximity decile, session and lateral distance bin, in standard-deviation (SD) units. We applied the same code to the MICrONS functional connectomics release. Results: in MICrONS (V1 to V1, in vivo movie signal correlation, 2,840 connections) the effect was 0.147 SD (95% CI 0.103-0.183), and 0.180 SD for L2/3 and L4 presynaptic cells. In V1DD it was 0.022 SD (-0.021-0.066) with deconvolved events and 0.053 SD (0.007-0.101) with dF/F; for L2/3 and L4 presynaptic cells 0.057 and 0.092 SD; L5 presynaptic cells showed none. The V1DD effect was 15-51% of the MICrONS effect (bootstrap p = 0.0005-0.022). Our proximity proxy gave an equal or larger MICrONS effect (0.159 SD) than skeleton co-travel, response reliability was equal (median CC_max 0.64 in both), and MICrONS samples of the V1DD size detected the effect 200 of 200 times. Gratings, natural images, sparse-noise maps and orientation preference also gave effects below 0.06 SD in V1DD. Connected same-session V1DD pairs had slightly higher movie noise correlations (0.07 SD, p = 0.025). Multi-synapse pairs were more similar than single-synapse pairs in both mice. Main limitations: V1DD coregistration errors cannot be measured; stimuli (one 120 s movie versus six 10 s clips) and sampled depths differ; two animals cannot give the distribution across mice. Conclusion: the rule replicates in direction for L2/3 and L4 presynaptic neurons, but the single-animal MICrONS effect size is not general.

functional connectomics · like-to-like connectivity · V1 Deep Dive · V1DD · MICrONS · mouse visual cortex · electron microscopy · two-photon imaging · signal correlation · replication · axon-dendrite proximity · coregistration

Admitted 11 citing publications

References

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

    We use the Ding et al. 2025 MICrONS functional connectomics release (node and edge tables) as the reference, and we test whether its like-to-like effect size repeats in a second mouse. The direction repeats; the size is 2 to 7 times smaller in V1DD.

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

    We use the MICrONS minnie65 v1507 synapse table to compute our synapse-site proximity proxy in MICrONS.

  3. In MICrONS mouse visual cortex, connected excitatory neurons had more similar preferred orientations mainly when their synapses were large (14,412 neurons, digital-twin tuning) sci:sha256:07b8a9b83eea2b7443dc99d29805440aefc0d23414bb9c8959decc534824bd92

    Earlier SCI study of orientation like-to-like wiring and synapse size in MICrONS only; our study adds a second mouse.

  4. Excitatory axons, but not basket cell axons, selected excitatory targets with similar orientation beyond axon–dendrite overlap and 10 µm soma distance in MICrONS mouse visual cortex sci:sha256:3475d3289a96669e6e83d55e0fc9ec509894213422121532387c543739c8dca2

    Earlier SCI study of excitatory and basket-cell output specificity in MICrONS only.

  5. usesdoi:10.3389/fncom.2016.00010

    We use the CC_max reliability measure of Schoppe et al. 2016, as MICrONS did.

  6. doi:10.1038/nature09880

    First report of like-to-like connectivity in mouse V1 with paired recordings.

  7. doi:10.7554/eLife.38173

    CaImAn spike inference, used for the MICrONS in vivo responses.

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