title: Neuregulin 1-ErbB4 signaling in the bed nucleus of the stria terminalis regulates anxiety-like behavior.
abstract: The bed nucleus of the stria terminalis (BNST), a nucleus defined as part of the extended amygdala, is involved in the expression of anxiety disorders. However, the regulatory mechanisms of BNST inhibitory activity that is involved in anxiety are unknown. Here, we showed that blocking neuregulin 1 (NRG1)-ErbB4 signaling in the BNST of mice, by either neutralizing endogenous NRG1 with ecto-Erbb4 or antagonizing the ErbB4 receptor with its specific inhibitor, produced anxiogenic responses. Interestingly, application of exogenous NRG1 into the BNST induced no anxiolytic effects, suggesting saturating activity of endogenous NRG1. While infusion of the GABAA receptor antagonist bicuculline into the BNST also led to anxiety-related behaviors, it did not worsen the anxiogenic effects produced by blocking NRG1-ErbB4 signaling, suggesting possible involvement of GABAergic neurotransmission. Further, in vitro electrophysiological recordings showed that BNST NRG1-ErbB4 signaling regulated the presynaptic GABA release. Together, these results suggest that NRG1-ErbB4 signaling in the BNST may play an important role in regulating anxiety-like behaviors.
authors.affiliation: State Key Laboratory of Organ Failure Research, Key Laboratory of Psychiatric Disorders of Guangdong Province, Collaborative Innovation Center for Brain Science, Department of Neurobiology, Southern Medical University, Guangzhou 510515, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Geng
authors.affiliation: State Key Laboratory of Organ Failure Research, Key Laboratory of Psychiatric Disorders of Guangdong Province, Collaborative Innovation Center for Brain Science, Department of Neurobiology, Southern Medical University, Guangzhou 510515, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Organ Failure Research, Key Laboratory of Psychiatric Disorders of Guangdong Province, Collaborative Innovation Center for Brain Science, Department of Neurobiology, Southern Medical University, Guangzhou 510515, China.
authors.forename: Jian-Lin
authors.initials: JL
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Organ Failure Research, Key Laboratory of Psychiatric Disorders of Guangdong Province, Collaborative Innovation Center for Brain Science, Department of Neurobiology, Southern Medical University, Guangzhou 510515, China.
authors.forename: Wen-Jun
authors.initials: WJ
authors.lastname: Zou
authors.affiliation: State Key Laboratory of Organ Failure Research, Key Laboratory of Psychiatric Disorders of Guangdong Province, Collaborative Innovation Center for Brain Science, Department of Neurobiology, Southern Medical University, Guangzhou 510515, China.
authors.forename: Zhi-Ping
authors.initials: ZP
authors.lastname: Liang
authors.affiliation: State Key Laboratory of Organ Failure Research, Key Laboratory of Psychiatric Disorders of Guangdong Province, Collaborative Innovation Center for Brain Science, Department of Neurobiology, Southern Medical University, Guangzhou 510515, China.
authors.forename: Lin-Lin
authors.initials: LL
authors.lastname: Bi
authors.affiliation: State Key Laboratory of Organ Failure Research, Key Laboratory of Psychiatric Disorders of Guangdong Province, Collaborative Innovation Center for Brain Science, Department of Neurobiology, Southern Medical University, Guangzhou 510515, China.
authors.forename: Ji-Hong
authors.initials: JH
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Organ Failure Research, Key Laboratory of Psychiatric Disorders of Guangdong Province, Collaborative Innovation Center for Brain Science, Department of Neurobiology, Southern Medical University, Guangzhou 510515, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Kong
authors.affiliation: State Key Laboratory of Organ Failure Research, Key Laboratory of Psychiatric Disorders of Guangdong Province, Collaborative Innovation Center for Brain Science, Department of Neurobiology, Southern Medical University, Guangzhou 510515, China.
authors.forename: Chu-Qiang
authors.initials: CQ
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Organ Failure Research, Key Laboratory of Psychiatric Disorders of Guangdong Province, Collaborative Innovation Center for Brain Science, Department of Neurobiology, Southern Medical University, Guangzhou 510515, China.
authors.forename: Xiao-Wen
authors.initials: XW
authors.lastname: Li
authors.affiliation: State Key Laboratory of Organ Failure Research, Key Laboratory of Psychiatric Disorders of Guangdong Province, Collaborative Innovation Center for Brain Science, Department of Neurobiology, Southern Medical University, Guangzhou 510515, China.
authors.forename: Jian-Ming
authors.initials: JM
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Organ Failure Research, Key Laboratory of Psychiatric Disorders of Guangdong Province, Collaborative Innovation Center for Brain Science, Department of Neurobiology, Southern Medical University, Guangzhou 510515, China. Electronic address: tgao@smu.edu.cn.
authors.forename: Tian-Ming
authors.initials: TM
authors.lastname: Gao
mesh_terms: D000818:Animals; D001007:Anxiety / Q000378:metabolism*; D001640:Bicuculline / Q000494:pharmacology; D002491:Central Nervous System Agents / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D020890:Neuregulin-1 / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology; D066247:Receptor, ErbB-4 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000378:metabolism; D012686:Septal Nuclei / Q000187:drug effects / Q000378:metabolism*; D046509:Tissue Culture Techniques; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: C107875:6-(methylamino)pyrido(3,4-d)pyrimidine; D002491:Central Nervous System Agents; D058787:GABA-A Receptor Antagonists; D020890:Neuregulin-1; C490581:Nrg1 protein, mouse; D011743:Pyrimidines; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; C587690:Erbb4 protein, mouse; D066247:Receptor, ErbB-4; D001640:Bicuculline
keywords: BNST; ErbB4; GABAergic neurotransmission; NRG1; anxiety