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Unique versus Redundant Functions of Neuroligin Genes in Shaping Excitatory and Inhibitory Synapse Properties

Overview of attention for article published in Journal of Neuroscience, June 2017
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  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (80th percentile)
  • Above-average Attention Score compared to outputs of the same age and source (57th percentile)

Mentioned by

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19 tweeters

Citations

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25 Dimensions

Readers on

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100 Mendeley
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1 CiteULike
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Title
Unique versus Redundant Functions of Neuroligin Genes in Shaping Excitatory and Inhibitory Synapse Properties
Published in
Journal of Neuroscience, June 2017
DOI 10.1523/jneurosci.0125-17.2017
Pubmed ID
Authors

Soham Chanda, W. Dylan Hale, Bo Zhang, Marius Wernig, Thomas C. Südhof

Abstract

Neuroligins are evolutionarily conserved postsynaptic cell-adhesion molecules that interact with presynaptic neurexins. Neurons express multiple neuroligin isoforms that are targeted to specific synapses, but their synaptic functions and mechanistic redundancy are not completely understood. Overexpression or RNAi-mediated knockdown of neuroligins respectively causes dramatic increase or decrease in synapse density, whereas genetic deletions of neuroligins impair synapse function with only minor effects on synapse numbers, raising fundamental questions about the overall physiological role of neuroligins. Here, we have systematically analyzed the effects of conditional genetic deletions of all major neuroligin isoforms (i.e., NL1, NL2 and NL3), either individually or in combinations, in cultured mouse hippocampal and cortical neurons. We found that conditional genetic deletions of neuroligins caused no or only small change in synapses numbers, but strongly impaired synapse function. This impairment was isoform-specific, suggesting that neuroligins are not functionally redundant. Sparse neuroligin deletions produced phenotypes comparable to those of global deletions, indicating that neuroligins function in a cell-autonomous manner. Mechanistically, neuroligin deletions decreased the synaptic levels of neurotransmitter receptors, and had no effect on presynaptic release probabilities. Overexpression of neuroligin-1 in control or neuroligin-deficient neurons increased synaptic transmission and synapse density but not spine numbers, suggesting that these effects reflect a gain-of-function mechanism; whereas overexpression of neuroligin-3 (that like neuroligin-1 is also targeted to excitatory synapses) had no comparable effect. Our data demonstrate that neuroligins are required for the physiological organization of neurotransmitter receptors in postsynaptic specializations, and suggest that they do not play a major role in synapse formation.SIGNIFICANCE STATEMENTHuman neuroligin genes have been associated with autism, but the cellular functions of different neuroligins and their molecular mechanisms remain incompletely understood. Here, we performed comparative analyses in cultured mouse neurons of all major neuroligin isoforms, either individually or in combinations, using conditional knockouts. We found that neuroligin deletions did not affect synapse numbers, but differentially impaired excitatory or inhibitory synaptic functions in an isoform-specific manner. These impairments were due, at least in part, to a decrease in synaptic distribution of neurotransmitter receptors upon deletion of neuroligins. Conversely, overexpression of neuroligin-1 increased synapse but not spine numbers. Our results suggest that various neuroligin isoforms perform unique postsynaptic functions in organizing synapses but are not essential for synapse formation or maintenance.

Twitter Demographics

The data shown below were collected from the profiles of 19 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 100 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 1 1%
Unknown 99 99%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 35 35%
Researcher 19 19%
Unspecified 12 12%
Student > Master 8 8%
Student > Doctoral Student 7 7%
Other 18 18%
Unknown 1 1%
Readers by discipline Count As %
Neuroscience 38 38%
Agricultural and Biological Sciences 26 26%
Unspecified 18 18%
Biochemistry, Genetics and Molecular Biology 10 10%
Medicine and Dentistry 5 5%
Other 2 2%
Unknown 1 1%

Attention Score in Context

This research output has an Altmetric Attention Score of 9. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 19 August 2017.
All research outputs
#1,926,540
of 13,620,849 outputs
Outputs from Journal of Neuroscience
#4,093
of 18,767 outputs
Outputs of similar age
#52,331
of 264,335 outputs
Outputs of similar age from Journal of Neuroscience
#100
of 236 outputs
Altmetric has tracked 13,620,849 research outputs across all sources so far. Compared to these this one has done well and is in the 85th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 18,767 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 10.8. This one has done well, scoring higher than 78% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 264,335 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 80% of its contemporaries.
We're also able to compare this research output to 236 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 57% of its contemporaries.