title: Neuregulin 1/ErbB4 enhances synchronized oscillations of prefrontal cortex neurons via inhibitory synapses.
abstract: Both neuregulin 1 (NRG1) and its receptor ErbB4 are susceptibility genes for schizophrenia. Reduced synchronization of evoked oscillations in several cortical regions, especially in the prefrontal cortex, is associated with the core symptoms of schizophrenia. Recent studies have reported that NRG1 may affect the hippocampal oscillations. However, the role of NRG1/ErbB4 signaling in the synchronization of neurons in the prefrontal cortex is unclear. Here, we found that NRG1 enhanced the synchrony of pyramidal neurons via presynaptic interneurons. Meanwhile, NRG1 also increased the synchrony between pairs of fast-spiking interneurons and pairs of fast-spiking and non-fast-spiking interneurons in the prefrontal cortex, and this effect was mediated by ErbB4 receptors. Moreover, the NRG1-enhanced synchrony of interneurons was through their mutually-inhibitory synapses but not electrical coupling. Furthermore, kainate-induced gamma oscillations in vivo were enhanced by NRG1 and did not change in Dlx5/6-ErbB4(-/-) mice in which the ErbB4 receptors were specifically knocked out in interneurons of the frontal brain. Overall, our findings suggested that NRG1/ErbB4 signaling plays an important role in the synchronized oscillations of the whole network in the prefrontal cortex that are impaired in schizophrenia.
authors.affiliation: Institute of Neuroscience, Department of Neurobiology, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, Zhejiang Province Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.
authors.forename: X-J
authors.initials: XJ
authors.lastname: Hou
authors.affiliation: Institute of Neuroscience, Department of Neurobiology, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, Zhejiang Province Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.
authors.forename: K-M
authors.initials: KM
authors.lastname: Ni
authors.affiliation: Institute of Neuroscience, Department of Neurobiology, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, Zhejiang Province Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.
authors.forename: J-M
authors.initials: JM
authors.lastname: Yang
authors.affiliation: Institute of Neuroscience, Department of Neurobiology, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, Zhejiang Province Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China; Soft Matter Research Center, Zhejiang University, Hangzhou, Zhejiang 310058, China. Electronic address: lixm@zju.edu.cn.
authors.forename: X-M
authors.initials: XM
authors.lastname: Li
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D017629:Gap Junctions / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D007395:Interneurons / Q000187:drug effects / Q000502:physiology; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D020890:Neuregulin-1 / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010852:Picrotoxin / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000502:physiology*; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology; D066247:Receptor, ErbB-4; D013569:Synapses / Q000187:drug effects / Q000502:physiology*
chemical_list: D066246:ErbB Receptors; D018690:Excitatory Amino Acid Agonists; D018756:GABA Antagonists; D007608:Kainic Acid; D020890:Neuregulin-1; D010852:Picrotoxin; D066247:Receptor, ErbB-4; C587690:Erbb4 protein, mouse
keywords: ErbB4; gamma oscillations; inhibitory synapses; neuregulin 1; prefrontal cortex; synchrony