title: Regulation of spine formation by ErbB4 in PV-positive interneurons.
abstract: The trophic factor neuregulin 1 (Nrg1) and its receptor ErbB4 are schizophrenia candidate genes. NRG1-ErbB4 signaling was thought to regulate spine formation and function in a cell-autonomous manner. Yet, recent studies indicate that ErbB4 expression is largely restricted to GABAergic interneurons and is very low or absent in pyramidal cells. Here, we generated and characterized cell type-specific ErbB4 mutant and transgenic mice. Spine density and the number of excitatory synapses were unaltered by neither deletion nor overexpression of ErbB4 in pyramidal neurons. However, spine density and excitatory synapse number were reduced in PV-ErbB4(-/-) mice where ErbB4 was selectively ablated in parvalbumin-positive GABAergic interneurons. Concurrently, basal glutamate transmission was impaired in PV-ErbB4(-/-) mice, but not in mice where ErbB4 was deleted or overexpressed in pyramidal neurons. Our results demonstrate a role of ErbB4 in PV-positive interneurons for spine formation in excitatory neurons.
authors.affiliation: Institute of Molecular Medicine and Genetics, Medical College of Georgia, Georgia Regents University, Augusta, Georgia 30912, Department of Neurobiology, Southern Medical University, Guangzhou, Guangdong, China, Department of Neurology, Medical College of Georgia, Georgia Regents University, Augusta, Georgia 30912, and Charlie Norwood Veterans Administration Medical Center, Augusta, Georgia 30912.
authors.forename: Dong-Min
authors.initials: DM
authors.lastname: Yin
authors.forename: Xiang-Dong
authors.initials: XD
authors.lastname: Sun
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Bean
authors.forename: Thiri W
authors.initials: TW
authors.lastname: Lin
authors.forename: Anupama
authors.initials: A
authors.lastname: Sathyamurthy
authors.forename: Wen-Cheng
authors.initials: WC
authors.lastname: Xiong
authors.forename: Tian-Ming
authors.initials: TM
authors.lastname: Gao
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Chen
authors.forename: Lin
authors.initials: L
authors.lastname: Mei
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D056547:CA1 Region, Hippocampal / Q000502:physiology / Q000648:ultrastructure; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D049229:Dendritic Spines / Q000502:physiology*; D055724:Electrophysiological Phenomena; D066246:ErbB Receptors / Q000235:genetics / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D007395:Interneurons / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D020890:Neuregulin-1 / Q000502:physiology; D010320:Parvalbumins / Q000502:physiology*; D017397:Prefrontal Cortex / Q000166:cytology / Q000502:physiology; D017966:Pyramidal Cells / Q000502:physiology; D066247:Receptor, ErbB-4; D005680:gamma-Aminobutyric Acid / Q000502:physiology
chemical_list: D020890:Neuregulin-1; C490581:Nrg1 protein, mouse; D010320:Parvalbumins; D005680:gamma-Aminobutyric Acid; D066246:ErbB Receptors; C587690:Erbb4 protein, mouse; D066247:Receptor, ErbB-4; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2
keywords: ErbB4; GABAergic; glutamatergic; neuregulin; schizophrenia; spine