Regulation of synapse development by Vgat deletion from ErbB4-positive interneurons

Thiri W. Lin, Zhibing Tan, Arnab Barik, Dong Min Yin, Egil Brudvik, Hongsheng Wang, Wen Cheng Xiong, Lin Mei

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5 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2533-2550
Number of pages18
JournalJournal of Neuroscience
Volume38
Issue number10
DOIs
Publication statusPublished - Mar 7 2018

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Keywords

  • Axo-axonic
  • Axo-somatic
  • ErbB4
  • GABA
  • Inhibition
  • Parvalbumin

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Lin, T. W., Tan, Z., Barik, A., Yin, D. M., Brudvik, E., Wang, H., ... Mei, L. (2018). Regulation of synapse development by Vgat deletion from ErbB4-positive interneurons. Journal of Neuroscience, 38(10), 2533-2550. https://doi.org/10.1523/JNEUROSCI.0669-17.2018