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PMID: 24305825 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Regulation of spine formation by ErbB4 in PV-positive interneurons.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 33 ·No. 49 ·2013-12-04 ·Pages 19295-303

Yin DM, Sun XD, Bean JC, Lin TW, Sathyamurthy A, Xiong WC, Gao TM, Chen YJ, Mei L

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.

Keywords
ErbB4 GABAergic glutamatergic neuregulin schizophrenia spine
MeSH Terms
Analysis of Variance Animals Blotting, Western CA1 Region, Hippocampal/physiology,ultrastructure Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism Dendritic Spines/physiology Electrophysiological Phenomena ErbB Receptors/genetics,physiology Fluorescent Antibody Technique Interneurons/physiology Mice Mice, Knockout Microscopy, Electron Neuregulin-1/physiology Parvalbumins/physiology Prefrontal Cortex/cytology,physiology Pyramidal Cells/physiology Receptor, ErbB-4 gamma-Aminobutyric Acid/physiology
Chemicals
Neuregulin-1 Nrg1 protein, mouse Parvalbumins gamma-Aminobutyric Acid ErbB Receptors Erbb4 protein, mouse Receptor, ErbB-4 Calcium-Calmodulin-Dependent Protein Kinase Type 2
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Yin Dong-Min
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.
Sun Xiang-Dong
Bean Jonathan C
Lin Thiri W
Sathyamurthy Anupama
Xiong Wen-Cheng
Gao Tian-Ming
Chen Yong-Jun
Mei Lin
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
DOI
10.1523/JNEUROSCI.2090-13.2013
Published
2013-12-04
Pages
19295-303
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC3850044
Subset
IM
External Links
PubMed source DOI: 10.1523/JNEUROSCI.2090-13.2013 PMC Full Text View journal details
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