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

Autism-associated Shank3 is essential for homeostatic plasticity and neuronal circuit stability

Vedakumar Tatavarty, Alejandro Torrado Pacheco, Heather Lin, Nathaniel J. Miska, Keith B. Hengen, Florence F. Wagner, Gina G. Turrigiano
doi: https://doi.org/10.1101/365445
Vedakumar Tatavarty
1Dept of Biology, Brandeis University, Waltham, MA 02493
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Alejandro Torrado Pacheco
1Dept of Biology, Brandeis University, Waltham, MA 02493
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Heather Lin
1Dept of Biology, Brandeis University, Waltham, MA 02493
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nathaniel J. Miska
1Dept of Biology, Brandeis University, Waltham, MA 02493
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Keith B. Hengen
1Dept of Biology, Brandeis University, Waltham, MA 02493
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Florence F. Wagner
2Stanley Center for Psychiatric Research, Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gina G. Turrigiano
1Dept of Biology, Brandeis University, Waltham, MA 02493
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: turrigiano@brandeis.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

Summary

Mutations in Shank3 are strongly associated with autism spectrum disorders and circuit disfunction, but a unified view of how Shank3 loss disrupts circuit function and excitability is lacking. Stabilizing, homeostatic forms of synaptic and intrinsic plasticity are critical for preventing circuit hyper- or hypo-excitability, leading us to ask whether Shank3 loss perturbs circuits by disrupting homeostatic plasticity. We show that Shank3 loss abolishes synaptic and intrinsic homeostatic plasticity, which can be rescued by lithium(Li), a drug with therapeutic potential in human Shankopathies. Further, Shank3 loss in vivo severely compromises the ability of visual cortical circuits to recover from perturbations to sensory drive. Our findings suggest that the loss of homeostatic compensation is a critical endophenotype that can explain a range of circuit disfunctions in Shankopathies.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Back to top
PreviousNext
Posted September 05, 2018.
Download PDF

Supplementary Material

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.
Autism-associated Shank3 is essential for homeostatic plasticity and neuronal circuit stability
(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
Autism-associated Shank3 is essential for homeostatic plasticity and neuronal circuit stability
Vedakumar Tatavarty, Alejandro Torrado Pacheco, Heather Lin, Nathaniel J. Miska, Keith B. Hengen, Florence F. Wagner, Gina G. Turrigiano
bioRxiv 365445; doi: https://doi.org/10.1101/365445
Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
Autism-associated Shank3 is essential for homeostatic plasticity and neuronal circuit stability
Vedakumar Tatavarty, Alejandro Torrado Pacheco, Heather Lin, Nathaniel J. Miska, Keith B. Hengen, Florence F. Wagner, Gina G. Turrigiano
bioRxiv 365445; doi: https://doi.org/10.1101/365445

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 (2516)
  • Biochemistry (4961)
  • Bioengineering (3458)
  • Bioinformatics (15159)
  • Biophysics (6876)
  • Cancer Biology (5372)
  • Cell Biology (7699)
  • Clinical Trials (138)
  • Developmental Biology (4514)
  • Ecology (7120)
  • Epidemiology (2059)
  • Evolutionary Biology (10203)
  • Genetics (7494)
  • Genomics (9761)
  • Immunology (4811)
  • Microbiology (13166)
  • Molecular Biology (5124)
  • Neuroscience (29332)
  • Paleontology (203)
  • Pathology (833)
  • Pharmacology and Toxicology (1459)
  • Physiology (2125)
  • Plant Biology (4728)
  • Scientific Communication and Education (1007)
  • Synthetic Biology (1336)
  • Systems Biology (4000)
  • Zoology (768)