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

143 Citations (Scopus)

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

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Neuregulin-1
Dendritic Spines
Central Nervous System
Spine
Clozapine
Glutamate Receptors
Aggression
Cerebral Cortex
Synapses
Cerebellum
Antipsychotic Agents
Hippocampus
Schizophrenia
Technology
Genes
Proteins

Keywords

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

ASJC Scopus subject areas

  • General

Cite this

Impaired maturation of dendritic spines without disorganization of cortical cell layers in mice lacking NRG1/ErbB signaling in the central nervous system. / Barros, Claudia S.; Calabrese, Barbara; Chamero, Pablo; Roberts, Amanda J.; Korzus, Ed; Lloyd, Kevin C K; Stowers, Lisa; Mayford, Mark; Halpain, Shelley; Müller, Ulrich.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 106, No. 11, 17.03.2009, p. 4507-4512.

Research output: Contribution to journalArticle

Barros, Claudia S. ; Calabrese, Barbara ; Chamero, Pablo ; Roberts, Amanda J. ; Korzus, Ed ; Lloyd, Kevin C K ; Stowers, Lisa ; Mayford, Mark ; Halpain, Shelley ; Müller, Ulrich. / Impaired maturation of dendritic spines without disorganization of cortical cell layers in mice lacking NRG1/ErbB signaling in the central nervous system. In: Proceedings of the National Academy of Sciences of the United States of America. 2009 ; Vol. 106, No. 11. pp. 4507-4512.
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