@article{6f5a8b7de64746d59dfb853b09f7c8b0,
title = "Regulation of synapse development by Vgat deletion from ErbB4-positive interneurons",
abstract = " GABA signaling has been implicated in neural development; however, in vivo genetic evidence is missing because mutant mice lacking GABA activity die prematurely. Here, we studied synapse development by ablating vesicular GABA transporter (Vgat) in ErbB4 + interneurons. We show that inhibitory axo-somatic synapses onto pyramidal neurons vary from one cortical layer to another; however, inhibitory synapses on axon initial segments (AISs) were similar across layers. Conversely, parvalbumin-positive (PV + )/ErbB4 + interneurons and PV-only interneurons receive a higher number of inhibitorysynapses from PV + ErbB4 + interneurons compared with ErbB4-only interneurons. Vgat deletion from ErbB4 + interneurons reduced axo-somatic or axo-axonic synapses from PV + ErbB4 + interneurons onto excitatory neurons. This effect was associated with corresponding changes in neurotransmission. However, the Vgat mutation seemed to have little effect on inhibitory synapses onto PV + and/or ErbB4 + interneurons. Interestingly, perineuronal nets, extracellular matrix structures implicated in maturation, survival, protection, and plasticity of PV + interneurons, were increased in the cortex of ErbB4-Vgat -/- mice. No apparent difference was observed between males and females. These results demonstrate that Vgat of ErbB4 + interneurons is essential for the development of inhibitory synapses onto excitatory neurons and suggest a role of GABA in circuit assembly.",
keywords = "Axo-axonic, Axo-somatic, ErbB4, GABA, Inhibition, Parvalbumin",
author = "Lin, {Thiri W.} and Zhibing Tan and Arnab Barik and Yin, {Dong Min} and Egil Brudvik and Hongsheng Wang and Xiong, {Wen Cheng} and Lin Mei",
note = "Funding Information: Received March 10, 2017; revised Jan. 22, 2018; accepted Jan. 29, 2018. Author contributions: T.W.L., W.-C.X., and L.M. designed research; T.W.L., Z.T., A.B., D.-M.Y., E.B., and H.W. performed research; T.W.L. and Z.T. analyzed data; T.W.L. and L.M. wrote the paper. This work was supported by grants from the National Institutes of Health (L.M., W.-C.X.) and the Department of Veterans Affairs (L.M., W-C.X.). We thank Dr. A. Stranahan (Augusta University) for training with Reconstruct software; Dr. K. Dhandapani (Augusta University) for the PSD-95 antibody; Dr. D. Cai (University of Michigan) and Dr. J. Rathfon (Nikon) for consultation and advice on confocal imaging and analysis; Dr. J. Albert (Case Western Reserve University)andDr.H.Xu(AugustaUniversity)forconsultationandhelpfuldiscussionsonposthocpowercalculation; Mei and Xiong laboratory members for helpful discussions and assistance; and J. Klein for drawing the mouse diagram. The authors declare no competing financial interests. *T.W.L. and Z.T. contributed equally to this work. CorrespondenceshouldbeaddressedtoLinMei,DepartmentofNeurosciences,SchoolofMedicine,CaseWestern Reserve University, 10900 Euclid Ave., Cleveland, OH 44106. E-mail: lin.mei@case.edu. DOI:10.1523/JNEUROSCI.0669-17.2018 Copyright {\textcopyright} 2018 the authors 0270-6474/18/382533-18$15.00/0 Funding Information: This work was supported by grants from the National Institutes of Health NIH100000002(L.M., W.-C.X.) and the Department of Veterans Affairs VA 100000738 (L.M., W-C.X.). We thank Dr. A. Stranahan (Augusta University) for training with Reconstruct software; Dr. K. Dhandapani (Augusta University) for the PSD-95 antibody; Dr. D. Cai (University of Michigan) and Dr. J. Rathfon (Nikon) for consultation and advice on confocal imaging and analysis; Dr. J. Albert (Case Western Reserve University) and Dr. H. Xu (Augusta University) for consultation and helpful discussions on post hoc power calculation; Mei and Xiong laboratory members for helpful discussions and assistance; and J. Klein for drawing the mouse diagram. Publisher Copyright: {\textcopyright} 2018 the authors.",
year = "2018",
month = mar,
day = "7",
doi = "10.1523/JNEUROSCI.0669-17.2018",
language = "English (US)",
volume = "38",
pages = "2533--2550",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "10",
}