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Loss of Neuroligin3 specifically downregulates retinal GABA_Aalpha2 receptors but does not impact direction selectivity

Lookup NU author(s): Dr Vidhyasankar Krishnamoorthy

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).

Abstract

The postsynaptic adhesion proteins Neuroligins (NLs) are essential for proper synapse function, and their alterations are associated with a variety of neurodevelopmental disorders. It is increasingly clear that each NL isoform occupies specific subsets of synapses and is able to regulate the function of discrete networks. Studies of NL2 and NL4 in the retina in particular have contributed towards uncovering their role in inhibitory synapse function. In this study we show that NL3 is also predominantly expressed at inhibitory postsynapses in the retinal inner plexiform layer (IPL), where it colocalizes with both GABA_A- and glycinergic receptor clusters in a 3:2 ratio. In the NL3 deletion-mutant (knockout or KO) mouse, we uncovered a dramatic reduction of the number of GABA_Aα2-subunit containing GABA_A receptor clusters at the IPL. Retinal activity was thereafter assessed in KO and wild-type (WT) littermates by multi-electrode-array recordings of the output cells of retina, the retinal ganglion cells (RGCs). RGCs in the NL3 KO showed reduced spontaneous activity and an altered response to white noise stimulation. Moreover, upon application of light flashes, the proportion of cells firing at light offset (OFF RGCs) was significantly lower in the NL3 KO compared to WT littermates, whereas the relative number of cells firing at light onset (ON RGCs) increased. Interestingly, although GABA_Aα2-bearing receptors have been related to direction-selective circuits of the retina, features of direction selective-retinal ganglion cells recorded remained unperturbed in the NL3 KO. Together our data underscore the importance of NL3 for the integrity of specific GABA_Aergic retinal circuits and identifies NL3 as an important regulator of retinal activity.

Publication metadata

Author(s): Hoon M, Krishnamoorthy V, Gollisch T, Falkenburger B, Varoqueaux F

Publication type: Article

Publication status: Published

Journal: PLoS One

Year: 2017

Volume: 12

Issue: 7

Online publication date: 14/07/2017

Acceptance date: 23/06/2017

Date deposited: 10/01/2018

ISSN (electronic): 1932-6203

Publisher: PLOS

URL: https://doi.org/10.1371/journal.pone.0181011

DOI: 10.1371/journal.pone.0181011

PubMed id: 28708891

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