Genetic labeling reveals novel cellular targets of schizophrenia susceptibility gene: Distribution of gaba and non-gaba erbb4-positive cells in adult mouse brain

Jonathan C. Bean, Thiri W. Lin, Anupama Sathyamurthy, Fang Liu, Dong Min Yin, Wen Cheng Xiong, Lin Mei

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

Neuregulin 1 (NRG1) and its receptor ErbB4 are schizophrenia risk genes. NRG1-ErbB4 signaling plays a critical role in neural development and regulates neurotransmission and synaptic plasticity. Nevertheless, its cellular targets remain controversial. ErbB4 was thought to express in excitatory neurons, although recent studies disputed this view. Using mice that express a fluorescent protein under the promoter of the ErbB4 gene, we determined in what cells ErbB4 is expressed and their identity. ErbB4 was widely expressed in the mouse brain, being highest in amygdala and cortex. Almost all ErbB4-positive cells were GABAergic in cortex, hippocampus, basal ganglia, and most of amygdala in neonatal and adult mice, suggesting GABAergic transmission as a major target of NRG1-ErbB4 signaling in these regions. Non-GABAergic, ErbB4-positive cells were present in thalamus, hypothalamus, midbrain, and hindbrain. In particular, ErbB4 is expressedinserotoninergicneurons of raphenuclei but not innorepinephrinergicneurons of thelocus ceruleus. Inhypothalamus, ErbB4 is present in neurons that express oxytocin. Finally, ErbB4 is expressed in a group of cells in the subcortical areas that are positive for S100 calcium binding protein β. These results identify novel cellular targets of NRG1-ErbB4 signaling.

Original languageEnglish (US)
Pages (from-to)13549-13566
Number of pages18
JournalJournal of Neuroscience
Volume34
Issue number40
DOIs
StatePublished - Oct 1 2014

Keywords

  • ErbB4
  • NRG1
  • Neuregulin
  • Oxytocin
  • S100
  • Serotonin

ASJC Scopus subject areas

  • Neuroscience(all)

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