Retinal horizontal cells use different synaptic sites for global feedforward and local feedback signaling

Behrens, C.; Zhang, Y.; Yadav, S. C.; Haverkamp, S.; Irsen, S.; Korympidou, M. M.; Schaedler, A.; Dedek, K.; Smith, R. G.; Euler, T.; Berens, P.; Schubert, T.

doi:10.1101/780031

bioRxiv · 10.1101/780031

Retinal horizontal cells use different synaptic sites for global feedforward and local feedback signaling

Behrens, C.·Zhang, Y.·Yadav, S. C.·Haverkamp, S.·Irsen, S.·Korympidou, M. M.·Schaedler, A.·Dedek, K.·Smith, R. G.·Euler, T.·Berens, P.·Schubert, T.

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Abstract

In the outer plexiform layer (OPL) of the mouse retina, two types of cone photoreceptors (cones) provide input to more than a dozen types of cone bipolar cells (CBCs). This transmission is modulated by a single horizontal cell (HC) type, the only interneuron in the outer retina. Horizontal cells form feedback synapses with cones and feedforward synapses with CBCs. However, the exact computational role of HCs is still debated. Along with performing global signaling within their laterally coupled network, HCs also provide local, cone-specific feedback. Specifically, it has not been clear which synaptic structures HCs use to provide local feedback to cones and global forward signaling to CBCs.\n\nHere, we reconstructed in a serial block-face electron microscopy volume the dendritic trees of five HCs as well as cone axon terminals and CBC dendrites to quantitatively analyze their connectivity. In addition to the fine HC dendritic tips invaginating cone axon terminals, we also identified \"bulbs\", short segments of increased dendritic diameter on the primary dendrites of HCs. These bulbs are located well below the cone axon terminal base and make contact to other cells mostly identified as other HCs or CBCs. Using immunolabeling we show that HC bulbs express vesicular gamma-aminobutyric acid transporters and co-localize with GABA receptor {gamma}2 subunits. Together, this suggests the existence of two synaptic strata in the mouse OPL, spatially separating cone-specific feedback and feedforward signaling to CBCs. A biophysics-based computational model of a HC dendritic branch supports the hypothesis that the spatial arrangement of synaptic contacts allows simultaneous local feedback and global feedforward signaling.

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Behrens, C., Zhang, Y., Yadav, S. C., Haverkamp, S., Irsen, S., Korympidou, M. M., Schaedler, A., Dedek, K., Smith, R. G., Euler, T., Berens, P., Schubert, T.. 2019-09-24. Retinal horizontal cells use different synaptic sites for global feedforward and local feedback signaling. https://doi.org/10.1101/780031

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