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Ube3a is required for experience-dependent maturation of the neocortex.

Nature neuroscience | Jun 3, 2009

http://www.ncbi.nlm.nih.gov/pubmed/19430469

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.

Pubmed ID: 19430469 RIS Download

Mesh terms: Aging | Angelman Syndrome | Animals | Animals, Newborn | Cell Differentiation | Disease Models, Animal | Dominance, Ocular | Learning | Mice | Mice, Knockout | Neocortex | Neuronal Plasticity | Sensory Deprivation | Ubiquitin-Protein Ligases | Visual Cortex | Visual Pathways | Visual Perception

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Associated grants

  • Agency: NIA NIH HHS, Id: AG024492
  • Agency: NINDS NIH HHS, Id: NS035527
  • Agency: NINDS NIH HHS, Id: NS039402
  • Agency: NIA NIH HHS, Id: R01 AG024492
  • Agency: NIA NIH HHS, Id: R01 AG024492-05
  • Agency: NEI NIH HHS, Id: R01 EY018323
  • Agency: NEI NIH HHS, Id: R01 EY018323-02
  • Agency: NINDS NIH HHS, Id: R01 NS035527
  • Agency: NINDS NIH HHS, Id: R01 NS035527-09
  • Agency: NINDS NIH HHS, Id: R01 NS039402
  • Agency: NINDS NIH HHS, Id: R01 NS039402-10
  • Agency: NEI NIH HHS, Id: R01EY018323
  • Agency: NICHD NIH HHS, Id: T32 HD040127
  • Agency: NICHD NIH HHS, Id: T32 HD040127-09
  • Agency: NICHD NIH HHS, Id: T32-HD40127
  • Agency: Howard Hughes Medical Institute, Id:
  • Agency: Howard Hughes Medical Institute, Id:

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