title: Conserved interneuron-specific ErbB4 expression in frontal cortex of rodents, monkeys, and humans: implications for schizophrenia.
abstract: BACKGROUND
  Neuregulin-1 and ErbB4 are genetically associated with schizophrenia, and detailed knowledge of the cellular and subcellular localization of ErbB4 is important for understanding how neuregulin-1 regulates neuronal network activity and behavior. Expression of ErbB4 is restricted to interneurons in the rodent hippocampus and cortex. However, controversy remains about the cellular expression pattern in primate brain and its subcellular distribution in postsynaptic somatodendritic locations versus presynaptic terminals.
  
  
  METHODS
  ErbB4 expression was analyzed in pyramidal cells and interneurons in the frontal cortex of five species: C57BL6 mice (n = 3), ErbB4⁻/⁻ mice (n = 2), Sprague-Dawley rats (n = 3), two macaque species (n = 3 + 2), and humans (normal control subjects, n = 2). We investigated 1) messenger RNA in mice, macaques, and humans; 2) protein expression in all species using highly specific monoclonal antibodies; and 3) specificity tests of several ErbB4 antibodies on brain samples (mouse, macaque, human).
  
  
  RESULTS
  ErbB4 RNA is restricted to interneurons in the frontal cortex of mice. ErbB4 protein is undetectable in pyramidal cells of rodents, macaques, and human frontal cortex, whereas most interneurons positive for parvalbumin, calretinin, or cholecystokinin, but only a minority of calbindin-positive cells, co-express ErbB4 in macaques. Importantly, no presynaptic ErbB4 expression was detected in any species.
  
  
  CONCLUSIONS
  The interneuron-selective somatodendritic expression of ErbB4 is consistent with a primary role of neuregulin-ErbB4 signaling in the postsynaptic modulation of gamma-aminobutyric acidergic function in rodents and primates. Our data validate the use of rodents to analyze effects of abnormal ErbB4 function as a means to model endophenotypes of psychiatric disorders.
authors.affiliation: Section on Molecular Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Jörg
authors.initials: J
authors.lastname: Neddens
authors.forename: Kenneth N
authors.initials: KN
authors.lastname: Fish
authors.forename: Ludovic
authors.initials: L
authors.lastname: Tricoire
authors.forename: Detlef
authors.initials: D
authors.lastname: Vullhorst
authors.forename: Alon
authors.initials: A
authors.lastname: Shamir
authors.forename: Wonjae
authors.initials: W
authors.lastname: Chung
authors.forename: David A
authors.initials: DA
authors.lastname: Lewis
authors.forename: Chris J
authors.initials: CJ
authors.lastname: McBain
authors.forename: Andrés
authors.initials: A
authors.lastname: Buonanno
mesh_terms: D000818:Animals; D066246:ErbB Receptors / Q000096:biosynthesis*; D005625:Frontal Lobe / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D007395:Interneurons / Q000378:metabolism*; D008251:Macaca; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017729:Presynaptic Terminals / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism; D017966:Pyramidal Cells / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D066247:Receptor, ErbB-4; D012559:Schizophrenia / Q000378:metabolism*
chemical_list: D020033:Protein Isoforms; C587689:ERBB4 protein, human; D066246:ErbB Receptors; C587690:Erbb4 protein, mouse; C587691:Erbb4 protein, rat; D066247:Receptor, ErbB-4