Synapse maintenance and restoration in the retina by NGL2

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Abstract

Synaptic cell adhesion molecules (CAMs) promote synapse formation in the developing nervous system. To what extent they maintain and can restore connections in the mature nervous system is unknown. Furthermore, how synaptic CAMs affect the growth of synapse-bearing neurites is unclear. Here, we use adeno-associated viruses (AAVs) to delete, re-, and overexpress the synaptic CAM NGL2 in individual retinal horizontal cells. When we removed NGL2 from horizontal cells, their axons overgrew and formed fewer synapses, irrespective of whether Ngl2 was deleted during development or in mature circuits. When we re-expressed NGL2 in knockout mice, horizontal cell axon territories and synapse numbers were restored, even if AAVs were injected after phenotypes had developed. Finally, overexpression of NGL2 in wild-type horizontal cells elevated synapse numbers above normal levels. Thus, NGL2 promotes the formation, maintenance, and restoration of synapses in the developing and mature retina, and restricts axon growth throughout life.

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Florentina Soto

Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, Saint Louis, United States

For correspondence
sotof@wustl.edu

Competing interests
The authors declare that no competing interests exist.
Lei Zhao

Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, Saint Louis, United States

Competing interests
The authors declare that no competing interests exist.
Daniel Kerschensteiner

Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, Saint Louis, United States

For correspondence
kerschensteinerd@wustl.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-6794-9056

Funding

National Eye Institute (R01EY027411)

Florentina Soto
Daniel Kerschensteiner

National Eye Institute (R01EY026978)

Daniel Kerschensteiner

National Eye Institute (R01EY023341)

Daniel Kerschensteiner

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All procedures were approved by the Animal Studies Committee of Washington University School (protocol # 20170033) of Medicine and performed in compliance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.