De novo synaptogenesis induced by GABA in the developing mouse cortex

Science. 2016 Sep 2;353(6303):1037-1040. doi: 10.1126/science.aaf5206. Epub 2016 Aug 11.

Abstract

Dendrites of cortical pyramidal neurons contain intermingled excitatory and inhibitory synapses. We studied the local mechanisms that regulate the formation and distribution of synapses. We found that local γ-aminobutyric acid (GABA) release on dendrites of mouse cortical layer 2/3 pyramidal neurons could induce gephyrin puncta and dendritic spine formation via GABA type A receptor activation and voltage-gated calcium channels during early postnatal development. Furthermore, the newly formed inhibitory and excitatory synaptic structures rapidly gained functions. Bidirectional manipulation of GABA release from somatostatin-positive interneurons increased and decreased the number of gephyrin puncta and dendritic spines, respectively. These results highlight a noncanonical function of GABA as a local synaptogenic element shaping the early establishment of neuronal circuitry in mouse cortex.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Carrier Proteins / metabolism
  • Cerebral Cortex / cytology
  • Cerebral Cortex / growth & development*
  • Dendrites / physiology
  • Dendritic Spines / physiology
  • Female
  • Interneurons / metabolism
  • Interneurons / physiology
  • Male
  • Membrane Proteins / metabolism
  • Mice
  • Neurogenesis*
  • Pyramidal Cells / metabolism
  • Pyramidal Cells / physiology*
  • Receptors, GABA-A / metabolism
  • Synapses / physiology*
  • gamma-Aminobutyric Acid / metabolism*

Substances

  • Carrier Proteins
  • Membrane Proteins
  • Receptors, GABA-A
  • gephyrin
  • gamma-Aminobutyric Acid