Impaired maturation of dendritic spines without disorganization of cortical cell layers in mice lacking NRG1/ErbB signaling in the central nervous system

Claudia S. Barros, Barbara Calabrese, Pablo Chamero, Amanda J. Roberts, Ed Korzus, Kent Lloyd, Lisa Stowers, Mark Mayford, Shelley Halpain, Ulrich Müller

Research output: Contribution to journalArticlepeer-review

Abstract

Neuregulin-1 (NRG1) and its ErbB2/B4 receptors are encoded by candidate susceptibility genes for schizophrenia, yet the essential functions of NRG1 signaling in the CNS are still unclear. Using CRE/LOX technology, we have inactivated ErbB2/B4-mediated NRG1 signaling specifically in the CNS. In contrast to expectations, cell layers in the cerebral cortex, hippocampus, and cerebellum develop normally in the mutant mice. Instead, loss of ErbB2/B4 impairs dendritic spine maturation and perturbs interactions of postsynaptic scaffold proteins with glutamate receptors. Conversely, increased NRG1 levels promote spine maturation. ErbB2/B4-deficient mice show increased aggression and reduced prepulse inhibition. Treatment with the antipsychotic drug clozapine reverses the behavioral and spine defects. We conclude that ErbB2/B4-mediated NRG1 signaling modulates dendritic spine maturation, and that defects at glutamatergic synapses likely contribute to the behavioral abnormalities in ErbB2/ B4-deficient mice.

Original languageEnglish (US)
Pages (from-to)4507-4512
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number11
DOIs
StatePublished - Mar 17 2009

Keywords

  • Cerebral cortex
  • Dendritic spines
  • Migration
  • Neuregulin
  • Schizophrenia

ASJC Scopus subject areas

  • General

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