Autism-Associated Shank3 Is Essential for Homeostatic Compensation in Rodent V1

Vedakumar Tatavarty, Alejandro Torrado Pacheco, Chelsea Groves Kuhnle, Heather Lin, Priya Koundinya, Nathaniel J. Miska, Keith B. Hengen, Florence F. Wagner, Stephen D. Van Hooser, Gina G. Turrigiano

Research output: Contribution to journalArticlepeer-review

71 Scopus citations

Abstract

Mutations in Shank3 are strongly associated with autism spectrum disorders and neural circuit changes in several brain areas, but the cellular mechanisms that underlie these defects are not understood. Homeostatic forms of plasticity allow central circuits to maintain stable function during experience-dependent development, leading us to ask whether loss of Shank3 might impair homeostatic plasticity and circuit-level compensation to perturbations. We found that Shank3 loss in vitro abolished synaptic scaling and intrinsic homeostatic plasticity, deficits that could be rescued by treatment with lithium. Further, Shank3 knockout severely compromised the in vivo ability of visual cortical circuits to recover from perturbations to sensory drive. Finally, lithium treatment ameliorated a repetitive self-grooming phenotype in Shank3 knockout mice. These findings demonstrate that Shank3 loss severely impairs the ability of central circuits to harness homeostatic mechanisms to compensate for perturbations in drive, which, in turn, may render them more vulnerable to such perturbations.

Original languageEnglish
Pages (from-to)769-777.e4
JournalNeuron
Volume106
Issue number5
DOIs
StatePublished - Jun 3 2020

Keywords

  • ASD
  • GSK3
  • Shank3
  • homeostatic plasticity
  • intrinsic homeostatic plasticity
  • lithium
  • synaptic scaling
  • visual cortex

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