Retinal Horizontal Cells Use Different Synaptic Sites for Global Feedforward and Local Feedback Signaling

Authors

Christian Behrens
Shubhash Chandra Yadav
Maria M Korympidou
Yue Zhang
Silke Haverkamp
Stephan Irsen
Anna Schaedler
Xiaoyu Lu
Zhuohe Liu
Jan Lause
François St-Pierre
Katrin Franke
Anna Vlasits
Karin Dedek
Robert G Smith
Thomas Euler
Philipp Berens
Timm Schubert

Publication Date

2-7-2022

Journal

Current Biology

DOI

10.1016/j.cub.2021.11.055

PMID

34910950

PMCID

PMC8886496

PubMedCentral® Posted Date

2-7-2023

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes

Keywords

Animals, Feedback, Mammals, Mice, Retina, Retinal Cone Photoreceptor Cells, Retinal Horizontal Cells, Synapses

Abstract

In the outer plexiform layer (OPL) of the mammalian retina, cone photoreceptors (cones) provide input to more than a dozen types of cone bipolar cells (CBCs). 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 an 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 suggest 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.

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