Letter | Published:

Sidekick 2 directs formation of a retinal circuit that detects differential motion

Nature volume 524, pages 466470 (27 August 2015) | Download Citation

Abstract

In the mammalian retina, processes of approximately 70 types of interneurons form specific synapses on roughly 30 types of retinal ganglion cells (RGCs) in a neuropil called the inner plexiform layer. Each RGC type extracts salient features from visual input, which are sent deeper into the brain for further processing1,2,3,4. The specificity and stereotypy of synapses formed in the inner plexiform layer account for the feature-detecting ability of RGCs. Here we analyse the development and function of synapses on one mouse RGC type, called the W3B-RGC5,6. These cells have the remarkable property of responding when the timing of the movement of a small object differs from that of the background, but not when they coincide6. Such cells, known as local edge detectors or object motion sensors, can distinguish moving objects from a visual scene that is also moving6,7,8,9,10,11,12. We show that W3B-RGCs receive strong and selective input from an unusual excitatory amacrine cell type known as VG3-AC (vesicular glutamate transporter 3). Both W3B-RGCs and VG3-ACs express the immunoglobulin superfamily recognition molecule sidekick 2 (Sdk2)13,14, and both loss- and gain-of-function studies indicate that Sdk2-dependent homophilic interactions are necessary for the selectivity of the connection. The Sdk2-specified synapse is essential for visual responses of W3B-RGCs: whereas bipolar cells relay visual input directly to most RGCs, the W3B-RGCs receive much of their input indirectly, via the VG3-ACs. This non-canonical circuit introduces a delay into the pathway from photoreceptors in the centre of the receptive field to W3B-RGCs, which could improve their ability to judge the synchrony of local and global motion.

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Acknowledgements

We thank E. Soucy and J. Greenwood for assistance with constructing the two-photon microscope, the Genome Modification Facility at Harvard for generating mouse lines, and E. Feinberg for insight into the ion selectivity of ChR2. This work was supported by grants from the NIH (NS029169 and EY022073) to J.R.S., NSERC (Canada) and Banting Postdoctoral Fellowships to A.K., a HHMI-Life Sciences Research Foundation Postdoctoral Fellowship to X.D., and an NIH fellowship (F31 NS055488) to Y.K.H.

Author information

Author notes

    • Arjun Krishnaswamy
    •  & Masahito Yamagata

    These authors contributed equally to this work.

    • Y. Kate Hong

    Present address: Department of Neuroscience, Columbia University, New York 10032, USA.

Affiliations

  1. Department of Molecular and Cellular Biology and Center for Brain Science, Harvard University, Cambridge, Massachusetts 02138, USA

    • Arjun Krishnaswamy
    • , Masahito Yamagata
    • , Xin Duan
    • , Y. Kate Hong
    •  & Joshua R. Sanes

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Contributions

A.K., M.Y. and J.R.S. planned experiments, analysed data and wrote the paper. A.K. performed electrophysiological and histological experiments, M.Y. performed genetic and histological experiments, X.D. developed methods and generated reagents and Y.K.H. generated reagents and performed in situ hybridization. The authors declare no competing interest.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Joshua R. Sanes.

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https://doi.org/10.1038/nature14682

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