Rac1 and rac3 GTPases control synergistically the development of cortical and hippocampal GABAergic interneurons

Cereb Cortex. 2014 May;24(5):1247-58. doi: 10.1093/cercor/bhs402. Epub 2012 Dec 20.


The intracellular mechanisms driving postmitotic development of cortical γ-aminobutyric acid (GABA)ergic interneurons are poorly understood. We have addressed the function of Rac GTPases in cortical and hippocampal interneuron development. Developing neurons express both Rac1 and Rac3. Previous work has shown that Rac1 ablation does not affect the development of migrating cortical interneurons. Analysis of mice with double deletion of Rac1 and Rac3 shows that these GTPases are required during postmitotic interneuron development. The number of parvalbumin-positive cells was affected in the hippocampus and cortex of double knockout mice. Rac depletion also influences the maturation of interneurons that reach their destination, with reduction of inhibitory synapses in both hippocampal CA1 and cortical pyramidal cells. The decreased number of cortical migrating interneurons and their altered morphology indicate a role of Rac1 and Rac3 in regulating the motility of cortical interneurons, thus interfering with their final localization. While electrophysiological passive and active properties of pyramidal neurons including membrane capacity, resting potential, and spike amplitude and duration were normal, these cells showed reduced spontaneous inhibitory currents and increased excitability. Our results show that Rac1 and Rac3 contribute synergistically to postmitotic development of specific populations of GABAergic cells, suggesting that these proteins regulate their migration and differentiation.

Keywords: GABAergic interneurons; Rac GTPases; cortex; hippocampus; neuronal migration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Aminopyridine / pharmacology
  • Animals
  • Animals, Newborn
  • Bicuculline / pharmacology
  • Cell Movement / drug effects
  • Cell Movement / genetics
  • Cerebral Cortex / cytology*
  • Excitatory Amino Acid Antagonists / pharmacology
  • GABA-A Receptor Antagonists / pharmacology
  • GABAergic Neurons / drug effects
  • GABAergic Neurons / physiology*
  • Gene Expression Regulation, Developmental / genetics
  • Hippocampus / cytology*
  • Inhibitory Postsynaptic Potentials / genetics
  • Interneurons / drug effects
  • Interneurons / physiology
  • Mice
  • Mice, Knockout
  • Piperazines / pharmacology
  • Potassium Channel Blockers / pharmacology
  • Vesicular Inhibitory Amino Acid Transport Proteins / metabolism
  • rac GTP-Binding Proteins / genetics
  • rac GTP-Binding Proteins / metabolism*
  • rac1 GTP-Binding Protein / genetics
  • rac1 GTP-Binding Protein / metabolism*


  • Excitatory Amino Acid Antagonists
  • GABA-A Receptor Antagonists
  • Piperazines
  • Potassium Channel Blockers
  • Vesicular Inhibitory Amino Acid Transport Proteins
  • Viaat protein, mouse
  • 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid
  • 4-Aminopyridine
  • Rac3 protein, mouse
  • rac GTP-Binding Proteins
  • rac1 GTP-Binding Protein
  • Bicuculline