title: Amygdala NRG1-ErbB4 is critical for the modulation of anxiety-like behaviors.
abstract: Anxiety disorder is related to the pathophysiology of psychiatric diseases, including major depression, substance abuse, and schizophrenia. The amygdala is important for manifestation and modulation of anxiety. However, relatively little is known regarding the mechanisms that control the amygdala inhibitory activity that is involved in anxiety. We found that almost all ErbB4, which is the only autonomous receptor of neuregulin 1 (NRG1) in the basolateral amygdala (BLA), was expressed in GABAergic neurons. Endogenous NRG1-ErbB4 signaling pathway in the BLA could modulate anxiety-like behaviors and GABA release, whereas it had no effect on glutamatergic transmission. The administration of NRG1 into the BLA of high-anxiety mice alleviated their anxiety and enhanced GABAergic neurotransmission. Moreover, exogenous NRG1 also produced an anxiolytic effect in the stressed mice. Together, these observations indicated that NRG1-ErbB4 signaling is critical to maintaining GABAergic activity in the amygdala and thus to modulating anxiety-like behaviors. Because NRG1 and ErbB4 are susceptibility genes of schizophrenia, our findings might also help to explain the potential mechanism of emotional abnormality in schizophrenia.
authors.affiliation: 1] State Key Laboratory of Organ Failure Research, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China [2] Key Laboratory of Psychiatric Disorders of Guangdong Province, Southern Medical University, Guangzhou, China [3] Institute for Brain Research, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Lin-Lin
authors.initials: LL
authors.lastname: Bi
authors.affiliation: 1] State Key Laboratory of Organ Failure Research, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China [2] Key Laboratory of Psychiatric Disorders of Guangdong Province, Southern Medical University, Guangzhou, China [3] Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Georgia Regents University, Augusta, GA, USA.
authors.forename: Xiang-Dong
authors.initials: XD
authors.lastname: Sun
authors.affiliation: 1] State Key Laboratory of Organ Failure Research, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China [2] Key Laboratory of Psychiatric Disorders of Guangdong Province, Southern Medical University, Guangzhou, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Georgia Regents University, Augusta, GA, USA.
authors.forename: Yi-Sheng
authors.initials: YS
authors.lastname: Lu
authors.affiliation: 1] State Key Laboratory of Organ Failure Research, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China [2] Key Laboratory of Psychiatric Disorders of Guangdong Province, Southern Medical University, Guangzhou, China.
authors.forename: Yi-Hua
authors.initials: YH
authors.lastname: Chen
authors.affiliation: 1] State Key Laboratory of Organ Failure Research, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China [2] Key Laboratory of Psychiatric Disorders of Guangdong Province, Southern Medical University, Guangzhou, China.
authors.forename: Jue
authors.initials: J
authors.lastname: Wang
authors.affiliation: 1] State Key Laboratory of Organ Failure Research, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China [2] Key Laboratory of Psychiatric Disorders of Guangdong Province, Southern Medical University, Guangzhou, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Geng
authors.affiliation: Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Georgia Regents University, Augusta, GA, USA.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.affiliation: 1] State Key Laboratory of Organ Failure Research, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China [2] Key Laboratory of Psychiatric Disorders of Guangdong Province, Southern Medical University, Guangzhou, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Zhang
authors.affiliation: 1] State Key Laboratory of Organ Failure Research, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China [2] Key Laboratory of Psychiatric Disorders of Guangdong Province, Southern Medical University, Guangzhou, China.
authors.forename: Ji-Hong
authors.initials: JH
authors.lastname: Liu
authors.affiliation: 1] State Key Laboratory of Organ Failure Research, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China [2] Key Laboratory of Psychiatric Disorders of Guangdong Province, Southern Medical University, Guangzhou, China.
authors.forename: Xiao-Wen
authors.initials: XW
authors.lastname: Li
authors.affiliation: 1] State Key Laboratory of Organ Failure Research, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China [2] Key Laboratory of Psychiatric Disorders of Guangdong Province, Southern Medical University, Guangzhou, China [3] Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Georgia Regents University, Augusta, GA, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Mei
authors.affiliation: 1] State Key Laboratory of Organ Failure Research, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China [2] Key Laboratory of Psychiatric Disorders of Guangdong Province, Southern Medical University, Guangzhou, China.
authors.forename: Tian-Ming
authors.initials: TM
authors.lastname: Gao
mesh_terms: D000679:Amygdala / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001007:Anxiety / Q000473:pathology* / Q000503:physiopathology*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D005247:Feeding Behavior / Q000187:drug effects; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009185:Myelin Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D000070816:Nogo Receptor 1; D011743:Pyrimidines / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology; D011930:Reaction Time / Q000187:drug effects / Q000235:genetics; D066247:Receptor, ErbB-4 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D020032:Tyrphostins / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: C107875:6-(methylamino)pyrido(3,4-d)pyrimidine; D004791:Enzyme Inhibitors; D058851:GPI-Linked Proteins; D009185:Myelin Proteins; D000070816:Nogo Receptor 1; D011743:Pyrimidines; D011799:Quinazolines; D011956:Receptors, Cell Surface; C419790:Rtn4r protein, mouse; D020032:Tyrphostins; C101044:RTKI cpd; D005680:gamma-Aminobutyric Acid; C587690:Erbb4 protein, mouse; D066247:Receptor, ErbB-4; D005968:Glutamate Decarboxylase