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In one mouse retina, bipolar kinetics read through dendrite depth predicted response transience of On ganglion cells (Spearman 0.58; polarity only −0.12), not of Off cells or within types

We asked which parts of the light response of a retinal ganglion cell (GC) follow from the depth of its dendrites in the inner plexiform layer. We used the e2198 mouse retina (electron microscopy and calcium imaging of the same tissue; 315 matched GCs of 47 types). For each GC we calculated the overlap of its dendrite depth profile with the EM terminal profiles of 12 cone bipolar cell (BC) types, and multiplied these weights by the glutamate responses of the same BC types from other mice (Franke et al. 2017). A rectifier and a calcium filter with two shared parameters gave the predicted response to a moving bar. We did not fit the response shape to GC data. sci:sha256:67b50cd7eac8ed362cb458cdee59d74b31defdd5bd3f9fbb91e3f01c79e3add7 tested the same type of model at the level of held-out types; our independent code reproduced its whole-trace result (mean cell r 0.778 vs 0.78; one mean On and one mean Off BC response did equally well). New results: (1) In 63 On cells of 18 types, the predicted On sustain index correlated with the measured index (Spearman 0.58, type-bootstrap 95% CI 0.07 to 0.73), but a polarity-only model gave -0.12 (difference CI 0.02 to 1.08). A glutamate depth map without BC labels gave 0.62, and all 864 possible cluster-to-type assignments gave 0.55 to 0.59. (2) No model predicted the Off sustain index of 93 Off cells (0.03). (3) For whole traces, the median r was 0.868; profiles of random cells gave 0.648 and profiles of same-class cells 0.841 (1,000 shuffles, p = 0.001); polarity only gave 0.853. (4) Inside types, structure added little: profiles of other same-type cells gave 0.863 (p = 0.11), and deviations from the type mean correlated weakly (mean r 0.047, p = 0.03). For scale, a depth kernel fitted on other types gave 0.910, the mean of other same-type cells 0.937, and split-half repeats 0.974. (5) The largest errors were in types whose polarity did not agree with their stratification, for example 5si (mostly On-layer dendrites, balanced On and Off responses) and F-mini On. Limitations: one retina; BC kinetics from other animals, another indicator and a chirp stimulus; depth overlap instead of synapse counts; no inhibition in the model; 0.128 s frames; responses averaged over directions. The package has code, derived tables, shuffle distributions, figures and source checksums; e2198 source files are not redistributed.

retina · retinal ganglion cell · bipolar cell · inner plexiform layer · stratification · structure and function · connectomics · electron microscopy · calcium imaging · iGluSnFR · e2198 · On and Off pathways · transient and sustained responses · zero-parameter model · reproduction

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References

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  1. In one mouse retina, dendrite depth predicted the polarity and part of the time course of 47 held-out ganglion cell types; bipolar-type overlap and bipolar kinetics added little sci:sha256:67b50cd7eac8ed362cb458cdee59d74b31defdd5bd3f9fbb91e3f01c79e3add7

    [Legacy relation: reproduces] Same e2198 cells and a priori BC-kernel model: our independent code reproduced its whole-trace result (mean cell r 0.778 vs 0.78; polarity-mean kernels equal) and the small effect of the 864 assignments. We add cell-level On/Off-specific kinetics, within-type and label-free tests.

  2. usesdoi:10.1016/j.cell.2018.04.040

    e2198 GC reconstructions, 47 types, stratification profiles and calcium-EM matches.

  3. usesdoi:10.1038/nature09818

    e2198 tissue and the two-photon calcium responses to moving bars.

  4. usesdoi:10.1038/nature21394

    BC glutamate responses by type (chirp), used as the BC kinetics.

  5. usesdoi:10.5061/dryad.rs2qp

    Franke et al. 2017 data file FrankeEtAl_BCs_2017_v1.mat (CC0).

  6. usesdoi:10.1038/nature13240

    Bipolar cell types reconstructed in e2198, whose depth profiles we use.

  7. doi:10.1016/j.celrep.2016.02.001

    e2198 BC types and sustained/transient input convergence.

  8. doi:10.1038/nature16468

    Functional GC types and the IPL depth hypothesis for response kinetics.

  9. doi:10.1038/35069068

    Stacked IPL representations: the depth code hypothesis we test.

  10. In one mouse retina, starburst contact direction predicted preferred motion direction within a median 12° for 26 On-Off and 23° for 7 transient On DS ganglion cells; arbor direction did not sci:sha256:d70a5a6322e8ec3db5b80f3d7871b4207590d3517332401bc14f8d9baeda0dc2

    Same e2198 cells; it found type-level but little cell-specific structural prediction of motion direction, which is compatible with our polarity and kinetics result.

  11. Local contact correction reduced motion prediction error in 27 cells from one mouse retina sci:sha256:be8277b484073d3a865b5e829d4dd0c2c24aaeedc71969d419baf8647372c367

    Same e2198 data set, starburst contact correction for direction prediction.

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