Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

The autism-associated gene Scn2a plays an essential role in synaptic stability and learning

Perry WE Spratt, Roy Ben-Shalom, Caroline M Keeshen, Kenneth J Burke Jr., Rebecca L Clarkson, View ORCID ProfileStephan J Sanders, Kevin J Bender
doi: https://doi.org/10.1101/366781
Perry WE Spratt
1Weill Institute for Neurosciences, University of California, San Francisco
2Department of Neurology, University of California, San Francisco
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Roy Ben-Shalom
1Weill Institute for Neurosciences, University of California, San Francisco
2Department of Neurology, University of California, San Francisco
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Caroline M Keeshen
1Weill Institute for Neurosciences, University of California, San Francisco
2Department of Neurology, University of California, San Francisco
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kenneth J Burke Jr.
1Weill Institute for Neurosciences, University of California, San Francisco
2Department of Neurology, University of California, San Francisco
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rebecca L Clarkson
1Weill Institute for Neurosciences, University of California, San Francisco
2Department of Neurology, University of California, San Francisco
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Stephan J Sanders
1Weill Institute for Neurosciences, University of California, San Francisco
3Department of Psychiatry, University of California, San Francisco
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Stephan J Sanders
Kevin J Bender
1Weill Institute for Neurosciences, University of California, San Francisco
2Department of Neurology, University of California, San Francisco
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Summary

Autism spectrum disorder (ASD) is strongly associated with de novo gene mutations. One of the most commonly affected genes is SCN2A. ASD-associated SCN2A mutations impair the encoded protein NaV1.2, a sodium channel important for action potential initiation and propagation in developing excitatory cortical neurons. The link between an axonal sodium channel and ASD, a disorder typically attributed to synaptic or transcriptional dysfunction, is unclear. Here, we show NaV1.2 is unexpectedly critical for dendritic excitability and synaptic function in mature pyramidal neurons, in addition to regulating early developmental axonal excitability. NaV1.2 loss reduced action potential backpropagation into dendrites, impairing synaptic plasticity and synaptic stability, even when NaV1.2 expression was disrupted late in development. Furthermore, we identified behavioral impairments in learning and sociability, paralleling observations in children with SCN2A loss. These results reveal a novel dendritic function for NaV1.2, providing insight into cellular mechanisms likely underlying circuit and behavioral dysfunction in ASD.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
Back to top
PreviousNext
Posted July 10, 2018.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
The autism-associated gene Scn2a plays an essential role in synaptic stability and learning
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
The autism-associated gene Scn2a plays an essential role in synaptic stability and learning
Perry WE Spratt, Roy Ben-Shalom, Caroline M Keeshen, Kenneth J Burke Jr., Rebecca L Clarkson, Stephan J Sanders, Kevin J Bender
bioRxiv 366781; doi: https://doi.org/10.1101/366781
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
The autism-associated gene Scn2a plays an essential role in synaptic stability and learning
Perry WE Spratt, Roy Ben-Shalom, Caroline M Keeshen, Kenneth J Burke Jr., Rebecca L Clarkson, Stephan J Sanders, Kevin J Bender
bioRxiv 366781; doi: https://doi.org/10.1101/366781

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Neuroscience
Subject Areas
All Articles
  • Animal Behavior and Cognition (3514)
  • Biochemistry (7371)
  • Bioengineering (5347)
  • Bioinformatics (20329)
  • Biophysics (10048)
  • Cancer Biology (7781)
  • Cell Biology (11353)
  • Clinical Trials (138)
  • Developmental Biology (6454)
  • Ecology (9985)
  • Epidemiology (2065)
  • Evolutionary Biology (13361)
  • Genetics (9377)
  • Genomics (12616)
  • Immunology (7729)
  • Microbiology (19119)
  • Molecular Biology (7478)
  • Neuroscience (41163)
  • Paleontology (301)
  • Pathology (1235)
  • Pharmacology and Toxicology (2142)
  • Physiology (3183)
  • Plant Biology (6885)
  • Scientific Communication and Education (1276)
  • Synthetic Biology (1900)
  • Systems Biology (5329)
  • Zoology (1091)