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GABA signaling promotes synapse elimination and axon pruning in developing cortical inhibitory interneurons.

Publication ,  Journal Article
Wu, X; Fu, Y; Knott, G; Lu, J; Di Cristo, G; Huang, ZJ
Published in: J Neurosci
January 4, 2012

Accumulating evidence indicates that GABA acts beyond inhibitory synaptic transmission and regulates the development of inhibitory synapses in the vertebrate brain, but the underlying cellular mechanism is not well understood. We have combined live imaging of cortical GABAergic axons across time scales from minutes to days with single-cell genetic manipulation of GABA release to examine its role in distinct steps of inhibitory synapse formation in the mouse neocortex. We have shown previously, by genetic knockdown of GABA synthesis in developing interneurons, that GABA signaling promotes the maturation of inhibitory synapses and axons. Here we found that a complete blockade of GABA release in basket interneurons resulted in an opposite effect, a cell-autonomous increase in axon and bouton density with apparently normal synapse structures. These results not only demonstrate that GABA is unnecessary for synapse formation per se but also uncover a novel facet of GABA in regulating synapse elimination and axon pruning. Live imaging revealed that developing GABAergic axons form a large number of transient boutons, but only a subset was stabilized. Release blockade led to significantly increased bouton stability and filopodia density, increased axon branch extension, and decreased branch retraction. Our results suggest that a major component of GABA function in synapse development is transmission-mediated elimination of subsets of nascent contacts. Therefore, GABA may regulate activity-dependent inhibitory synapse formation by coordinately eliminating certain nascent contacts while promoting the maturation of other nascent synapses.

Duke Scholars

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Published In

J Neurosci

DOI

EISSN

1529-2401

Publication Date

January 4, 2012

Volume

32

Issue

1

Start / End Page

331 / 343

Location

United States

Related Subject Headings

  • gamma-Aminobutyric Acid
  • Synapses
  • Organ Culture Techniques
  • Neurology & Neurosurgery
  • Neurogenesis
  • Neural Inhibition
  • Mice, Transgenic
  • Mice, Knockout
  • Mice
  • Male
 

Citation

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Wu, X., Fu, Y., Knott, G., Lu, J., Di Cristo, G., & Huang, Z. J. (2012). GABA signaling promotes synapse elimination and axon pruning in developing cortical inhibitory interneurons. J Neurosci, 32(1), 331–343. https://doi.org/10.1523/JNEUROSCI.3189-11.2012
Wu, Xiaoyun, Yu Fu, Graham Knott, Jiangteng Lu, Graziella Di Cristo, and Z Josh Huang. “GABA signaling promotes synapse elimination and axon pruning in developing cortical inhibitory interneurons.J Neurosci 32, no. 1 (January 4, 2012): 331–43. https://doi.org/10.1523/JNEUROSCI.3189-11.2012.
Wu X, Fu Y, Knott G, Lu J, Di Cristo G, Huang ZJ. GABA signaling promotes synapse elimination and axon pruning in developing cortical inhibitory interneurons. J Neurosci. 2012 Jan 4;32(1):331–43.
Wu, Xiaoyun, et al. “GABA signaling promotes synapse elimination and axon pruning in developing cortical inhibitory interneurons.J Neurosci, vol. 32, no. 1, Jan. 2012, pp. 331–43. Pubmed, doi:10.1523/JNEUROSCI.3189-11.2012.
Wu X, Fu Y, Knott G, Lu J, Di Cristo G, Huang ZJ. GABA signaling promotes synapse elimination and axon pruning in developing cortical inhibitory interneurons. J Neurosci. 2012 Jan 4;32(1):331–343.

Published In

J Neurosci

DOI

EISSN

1529-2401

Publication Date

January 4, 2012

Volume

32

Issue

1

Start / End Page

331 / 343

Location

United States

Related Subject Headings

  • gamma-Aminobutyric Acid
  • Synapses
  • Organ Culture Techniques
  • Neurology & Neurosurgery
  • Neurogenesis
  • Neural Inhibition
  • Mice, Transgenic
  • Mice, Knockout
  • Mice
  • Male