title: Maintenance of GABAergic activity by neuregulin 1-ErbB4 in amygdala for fear memory.
abstract: Inhibitory neurotransmission in amygdala is important for fear learning and memory. However, mechanisms that control the inhibitory activity in amygdala are not well understood. We provide evidence that neuregulin 1 (NRG1) and its receptor ErbB4 tyrosine kinase are critical for maintaining GABAergic activity in amygdala. Neutralizing endogenous NRG1, inhibition, or genetic ablation of ErbB4, which was expressed in a majority of palvalbumin (PV)+ neurons in amygdala, reduced GABAergic transmission and inhibited tone-cued fear conditioning. Specific ablation of ErbB4 in PV+ neurons reduced eIPSC/eEPSC ratios and impaired fear conditioning. Notably, expression of ErbB4 in amygdala was sufficient to diminish synaptic dysfunction and fear conditioning deficits in PV-ErbB4-/- mice. These observations indicated that NRG1 signaling maintains high GABAergic activity in amygdala and, thus, regulates fear memory. Considering that both NRG1 and ErbB4 are susceptibility genes of schizophrenia, our study sheds light on potential pathophysiological mechanisms of this disorder.
authors.affiliation: Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912, USA.
authors.forename: Yisheng
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912, USA; State Key Laboratory of Organ Failure Research, Key Laboratory of Psychiatric Disorders of Guangdong Province, Department of Neurobiology, Southern Medical University, Guangzhou 510515, China.
authors.forename: Xiang-Dong
authors.initials: XD
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Organ Failure Research, Key Laboratory of Psychiatric Disorders of Guangdong Province, Department of Neurobiology, Southern Medical University, Guangzhou 510515, China.
authors.forename: Feng-Qing
authors.initials: FQ
authors.lastname: Hou
authors.affiliation: State Key Laboratory of Organ Failure Research, Key Laboratory of Psychiatric Disorders of Guangdong Province, Department of Neurobiology, Southern Medical University, Guangzhou 510515, China.
authors.forename: Lin-Lin
authors.initials: LL
authors.lastname: Bi
authors.affiliation: Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912, USA; Key Laboratory of Brain Functional Genomics, Ministry of Education, Shanghai Key Laboratory of Brain Functional Genomics, School of Life Sciences, East China Normal University, Shanghai 200062, China.
authors.forename: Dong-Min
authors.initials: DM
authors.lastname: Yin
authors.affiliation: Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912, USA.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912, USA; Medical College of Acupuncture Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou 510407, China.
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Chen
authors.affiliation: Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912, USA.
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Bean
authors.affiliation: Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912, USA; Center for Neuropsychiatric Diseases, Institute of Life Science, Nanchang University, Nanchang 330031, China.
authors.forename: Hui-Feng
authors.initials: HF
authors.lastname: Jiao
authors.affiliation: Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912, USA.
authors.forename: Xihui
authors.initials: X
authors.lastname: Liu
authors.affiliation: Center for Neuropsychiatric Diseases, Institute of Life Science, Nanchang University, Nanchang 330031, China.
authors.forename: Bao-Ming
authors.initials: BM
authors.lastname: Li
authors.affiliation: Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912, USA; Department of Neurology, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912, USA; Charlie Norwood VA Medical Center, Augusta, GA 30912, USA.
authors.forename: Wen-Cheng
authors.initials: WC
authors.lastname: Xiong
authors.affiliation: State Key Laboratory of Organ Failure Research, Key Laboratory of Psychiatric Disorders of Guangdong Province, 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
authors.affiliation: Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912, USA; Department of Neurology, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912, USA; Charlie Norwood VA Medical Center, Augusta, GA 30912, USA; Center for Neuropsychiatric Diseases, Institute of Life Science, Nanchang University, Nanchang 330031, China. Electronic address: lmei@gru.edu.
authors.forename: Lin
authors.initials: L
authors.lastname: Mei
mesh_terms: D000679:Amygdala / Q000378:metabolism*; D000818:Animals; D003214:Conditioning, Classical / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005239:Fear / Q000502:physiology*; D053444:Inhibitory Postsynaptic Potentials / Q000502:physiology; D007395:Interneurons / Q000502:physiology; D008568:Memory / Q000502:physiology*; D051379:Mice; D020890:Neuregulin-1 / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D010320:Parvalbumins / Q000378:metabolism; D066247:Receptor, ErbB-4 / Q000378:metabolism*; D013569:Synapses / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D020890:Neuregulin-1; C490581:Nrg1 protein, mouse; D010320:Parvalbumins; D005680:gamma-Aminobutyric Acid; C587690:Erbb4 protein, mouse; D066247:Receptor, ErbB-4