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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

Question: does whole-brain wiring predict region-to-region functional connectivity (FC) in behaving Drosophila, does this coupling change between rest and walking, and does wiring from the matched transmitter class predict the FC of class-specific imaging lines better? Data: light-field calcium imaging of 75 brain regions (Aimon et al. 2023; 82 experiments; pan-neuronal, Cha, Gad, Vglut, TH, Trh and TDC lines) and the FlyWire v783 connectome (139,255 proofread neurons). Structural connectivity (SC) was the symmetric log synaptic flow between regions. We controlled for distance between region centroids and used flies as units. Results: group FC (50 flies) correlated with SC at Spearman rho = 0.48; distance-partial rho = 0.37, above a distance-stratified null (0.24 +/- 0.01; p < 0.0002). Distance alone explained R2 = 0.55 of group FC and SC added 0.06. In single flies the distance-partial coupling was 0.18 (95% CI 0.14-0.21) and positive in 48 of 50 flies; the between-fly FC agreement was rho = 0.58. Walking raised mean FC. Raw coupling was lower in walking by 0.013 to 0.036 in rho (clear only in the 20 flies with at least 60 s per state, p = 0.004). After global-signal regression the walk-rest difference was within +/-0.025 in all three state definitions (Wilcoxon p = 0.19 to 0.92). The walk-related FC change did not repeat between flies and did not follow SC. Coupling was highest in optic lobe, AMMC, SAD, IPS and GNG and lowest in the central complex and antennal lobe (split-half reliability rho = 0.86). Transmitter-matched SC gave no specific gain (permutation p = 0.37-0.66). Limitations: light-field blur can mix adjacent regions and distance control cannot remove all of it; connectome and activity come from different flies; states come from a convolved walk regressor; class SC matrices are highly correlated, so the class test has low power.

Drosophila · connectome · FlyWire · functional connectivity · structure-function coupling · light-field imaging · walking · brain state · neurotransmitter · global signal regression · neuropil

Admitted 13 citing publications

References

12
  1. usesdoi:10.7554/eLife.85202

    Source of the light-field regional calcium time series and walk regressors.

  2. usesdoi:10.5061/dryad.3bk3j9kpb

    Dryad record with the regional time series (Walk_anatomical_regions.zip).

  3. useshttps://github.com/sophie63/Aimon2022/tree/944c8367d5eed1a4ef477c702e31f31997762d34

    Regionsdf.pkl gives the fly identity of each experiment.

  4. usesdoi:10.1038/s41586-024-07558-y

    FlyWire whole-brain connectome.

  5. usesdoi:10.5281/zenodo.10676866

    FlyWire v783 per-neuron neuropil synapse counts and proofread neuron list.

  6. usesdoi:10.1038/s41586-024-07686-5

    FlyWire neuron annotations with transmitter labels.

  7. usesdoi:10.1016/j.cell.2024.03.016

    Synapse-level neurotransmitter predictions behind top_nt.

  8. usesdoi:10.5281/zenodo.10567

    JFRC2 neuropil meshes, used in FlyWire space for region centroids.

  9. useshttps://github.com/navis-org/fafbseg-py/tree/b62bed6572afb98ac6e64e738b8805341e7ee027

    Source of the neuropil meshes transformed to FlyWire space.

  10. supportsdoi:10.1016/j.cub.2021.03.004

    We extend their resting hemibrain SC-FC result to FlyWire, both hemispheres, light-field imaging and walking state.

  11. doi:10.1016/j.neuron.2013.12.017

    Neuropil nomenclature shared by both data sets.

  12. Tracer connection strength predicts spontaneous inter-areal spike correlations across mouse cortex beyond distance (24 mice, 30 areas), but not for visual to non-visual area pairs sci:sha256:cae100c0e7058b67d408e1b73c62b103dda4019ce6bef4f5dacabd46dea12f9b

    Related campaign result: tracer connectivity predicts spike correlations beyond distance in mouse cortex.

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