title: Development of GABA circuitry of fast-spiking basket interneurons in the medial prefrontal cortex of erbb4-mutant mice.
abstract: erbb4 is a susceptibility gene for schizophrenia and ErbB4 signals have been hypothesized to function in a number of cortical developmental processes (Silberberg et al., 2006; Mei and Xiong, 2008). Several recent studies show that the expression of ErbB4 is mainly restricted to GABAergic interneurons (Yau et al., 2003; Woo et al., 2007), specifically, to parvalbumin-positive (PV) fast-spiking (FS) interneurons (Vullhorst et al., 2009; Fazzari et al., 2010), a large majority of which are PV FS basket cells (Kawaguchi, 1995; Taniguchi et al., 2013). However, in the medial prefrontal cortex (mPFC), a brain region that is closely associated with neuropsychiatric disorders including schizophrenia, little is known about the roles of ErbB4 signals during the development of GABAergic circuitry particularly that associated with PV FS basket cells. Here, using molecular genetics, biochemistry, and electrophysiology, we deleted ErbB4 receptors in GABAergic forebrain neurons during the embryonic period and demonstrated that in the mouse mPFC, ErbB4 signals were dispensable for the development of GABAergic synapses by PV FS basket cells. Interestingly, they were required for the final maturation rather than the initial formation of glutamatergic synapses on PV FS basket cells. Furthermore, activity-dependent GABAergic PV FS pyramidal neuron transmission was decreased, whereas activity of pyramidal neurons was increased in KO mice. Together, these data indicate that ErbB4 signals contribute to the development of GABAergic circuitry associated with FS basket cells in component- and stage-dependent manners in the mPFC in vivo, and may suggest a mechanism for neuropsychiatric disorders including schizophrenia.
authors: Institute of Neuroscience, Key Laboratory of Medical Neurobiology of the Ministry of Health, Zhejiang Province Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China, 310058, Neurobiology Section, Division of Biological Sciences and Center for Neural Circuits and Behavior, University of California, San Diego, La Jolla, California 92093-0357, and Soft Matter Research Center, Zhejiang University, Hangzhou, Zhejiang, China, 310058.
authors: Jian-Ming
authors: JM
authors: Yang
authors: Jing
authors: J
authors: Zhang
authors: Xiao-Juan
authors: XJ
authors: Chen
authors: Hong-Yan
authors: HY
authors: Geng
authors: Mao
authors: M
authors: Ye
authors: Nicholas C
authors: NC
authors: Spitzer
authors: Jian-Hong
authors: JH
authors: Luo
authors: Shu-Min
authors: SM
authors: Duan
authors: Xiao-Ming
authors: XM
authors: Li
mesh_terms: D000818:Animals; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D007395:Interneurons / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009415:Nerve Net / Q000378:metabolism*; D010320:Parvalbumins / Q000378:metabolism; D017397:Prefrontal Cortex / Q000378:metabolism*; D017966:Pyramidal Cells / Q000378:metabolism; D066247:Receptor, ErbB-4; D013569:Synapses / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D010320:Parvalbumins; D005680:gamma-Aminobutyric Acid; D066246:ErbB Receptors; C587690:Erbb4 protein, mouse; D066247:Receptor, ErbB-4
keywords: ErbB4; GABAergic circuitry; development; medial prefrontal cortex (mPFC); parvalbumin (PV) interneurons; schizophrenia