Rac1 and Rac3 GTPases control synergistically the development of cortical and hippocampal GABAergic interneurons

Valentina Vaghi, Roberta Pennucci, Francesca Talpo, Sara Corbetta, Valentina Montinaro, Cinzia Barone, Laura Croci, Paolo Spaiardi, G. Giacomo Consalez, Gerardo Biella, Ivan De Curtis

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)1247-1258
Number of pages12
JournalCerebral Cortex
Volume24
Issue number5
DOIs
Publication statusPublished - 2014

Keywords

  • cortex
  • GABAergic interneurons
  • hippocampus
  • neuronal migration
  • Rac GTPases

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience
  • Medicine(all)

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    Vaghi, V., Pennucci, R., Talpo, F., Corbetta, S., Montinaro, V., Barone, C., Croci, L., Spaiardi, P., Consalez, G. G., Biella, G., & De Curtis, I. (2014). Rac1 and Rac3 GTPases control synergistically the development of cortical and hippocampal GABAergic interneurons. Cerebral Cortex, 24(5), 1247-1258. https://doi.org/10.1093/cercor/bhs402