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, Kevin C K Lloyd, Lisa Stowers, Mark Mayford, Shelley Halpain, Ulrich Müller

Research output: Contribution to journalArticle

146 Scopus citations

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

Fingerprint Dive into the research topics of 'Impaired maturation of dendritic spines without disorganization of cortical cell layers in mice lacking NRG1/ErbB signaling in the central nervous system'. Together they form a unique fingerprint.

  • Cite this