Article abstract


Nature Neuroscience 12, 777 - 783 (2009)
Published online: 10 May 2009 | doi:10.1038/nn.2327

Ube3a is required for experience-dependent maturation of the neocortex

Koji Yashiro1,8, Thorfinn T Riday1,2, Kathryn H Condon3, Adam C Roberts1,4,5, Danilo R Bernardo1, Rohit Prakash1, Richard J Weinberg4,6, Michael D Ehlers3,7 & Benjamin D Philpot1,2,4,5


Experience-dependent maturation of neocortical circuits is required for normal sensory and cognitive abilities, which are distorted in neurodevelopmental disorders. We tested whether experience-dependent neocortical modifications require Ube3a, an E3 ubiquitin ligase whose dysregulation has been implicated in autism and Angelman syndrome. Using visual cortex as a model, we found that experience-dependent maturation of excitatory cortical circuits was severely impaired in Angelman syndrome model mice deficient in Ube3a. This developmental defect was associated with profound impairments in neocortical plasticity. Normal plasticity was preserved under conditions of sensory deprivation, but was rapidly lost by sensory experiences. The loss of neocortical plasticity is reversible, as late-onset visual deprivation restored normal synaptic plasticity. Furthermore, Ube3a-deficient mice lacked ocular dominance plasticity in vivo when challenged with monocular deprivation. We conclude that Ube3a is necessary for maintaining plasticity during experience-dependent neocortical development and suggest that the loss of neocortical plasticity contributes to deficits associated with Angelman syndrome.

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  1. Department of Cell and Molecular Physiology University of North Carolina, Chapel Hill, North Carolina, USA.
  2. Curriculum in Neurobiology, University of North Carolina, Chapel Hill, North Carolina, USA.
  3. Department of Neurobiology, Duke University Medical Center, Durham, North Carolina, USA.
  4. University of North Carolina Neuroscience Center, University of North Carolina, Chapel Hill, North Carolina, USA.
  5. Neurodevelopmental Disorders Research Center, University of North Carolina, Chapel Hill, North Carolina, USA.
  6. Department of Cell and Developmental Biology, University of North Carolina, Chapel Hill, North Carolina, USA.
  7. Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina, USA.
  8. Present address: Urogenix, Inc., Durham, North Carolina, USA.

Correspondence to: Michael D Ehlers3,7 e-mail: ehlers@neuro.duke.edu

Correspondence to: Benjamin D Philpot1,2,4,5 e-mail: bphilpot@med.unc.edu



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