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

Retinal horizontal cells use different synaptic sites for global feedforward and local feedback signaling.
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DOI:
10.1016/j.cub.2021.11.055
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发表时间:
2022-02-07
期刊:
Current biology : CB
影响因子:
--
通讯作者:
Schubert T
Schubert T
中科院分区:
其他
文献类型:
--
作者:
Behrens C;Yadav SC;Korympidou MM;Zhang Y;Haverkamp S;Irsen S;Schaedler A;Lu X;Liu Z;Lause J;St-Pierre F;Franke K;Vlasits A;Dedek K;Smith RG;Euler T;Berens P;Schubert T

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In the outer plexiform layer (OPL) of the mammalian retina, cone photoreceptors (cones) provide input to more than a dozen types of cone bipolar cell (CBC). In the mouse, this transmission is modulated by a single horizontal cell (HC) type. HCs perform global signaling within their laterally coupled network, but also provide local, cone-specific feedback. However, it is unknown how HCs provide local feedback to cones at the same time as global forward signaling to CBCs and where the underlying synapses are located. To assess how HCs simultaneously perform different modes of signaling, we reconstructed the dendritic trees of five HCs as well as cone axon terminals and CBC dendrites in a serial block-face electron microscopy volume and analyzed 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 in a OPL stratum well below the cone axon terminal base and make contacts with other HCs and CBCs. Our results from immunolabeling, electron microscopy and glutamate imaging suggest that HC bulbs represent GABAergic synapses that do not receive any direct photoreceptor input. Together, our data suggests the existence of two synaptic strata in the mouse OPL, spatially separating cone-specific feedback and feedforward signaling to CBCs. A biophysical model of a HC dendritic branch and voltage imaging support the hypothesis that this spatial arrangement of synaptic contacts allows for simultaneous local feedback and global feedforward signaling by HCs. In the mammalian retina, it is unclear how horizontal cells provide both local feedback to photoreceptors and global forward signaling to bipolar cells simultaneously. Behrens et al. identify a second synaptic stratum in the outer mouse retina, spatially separating cone photoreceptor-specific feedback and feedforward signaling to bipolar cells.
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