Loss of Neuroligin3 specifically downregulates retinal GABAAα2 receptors without abolishing direction selectivity.

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Serval ID
serval:BIB_7C11E878C229
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Loss of Neuroligin3 specifically downregulates retinal GABAAα2 receptors without abolishing direction selectivity.
Journal
PloS one
Author(s)
Hoon M., Krishnamoorthy V., Gollisch T., Falkenburger B., Varoqueaux F.
ISSN
1932-6203 (Electronic)
ISSN-L
1932-6203
Publication state
Published
Issued date
2017
Peer-reviewed
Oui
Volume
12
Number
7
Pages
e0181011
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
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 GABAA- 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 GABAAα2-subunit containing GABAA 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 GABAAα2-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 GABAAergic retinal circuits and identifies NL3 as an important regulator of retinal activity.

Pubmed
Web of science
Open Access
Yes
Create date
28/08/2017 8:31
Last modification date
20/08/2019 14:37
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