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 isknownabout 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 periodanddemonstrated that in the mousem PFC,ErbB4 signal swere dispensable for the development of GABA ergic synapsesby PVFS basket cells. Interestingly,they were required for the finalmaturation rather than the initial formation of glutamatergic synapseson PVFS basket cells.Furthermore, activity-dependent GABA ergic PVFS pyramidal neuron transmission was decreased, whereas activity of pyramidal neurons was increased in KOmice. Together,these data indicate that ErbB4 signals contribute to the developmen to fGABA ergic circuitry associated with FS basket cells incomponent-and stage-dependentmannersin themPFCin vivo,andmaysuggest amechanism for neuropsychiatric disorders including schizophrenia. © 2013 the authors.