title: Rac1 and rac3 GTPases control synergistically the development of cortical and hippocampal GABAergic interneurons.
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.
authors.affiliation: Division of Neuroscience, San Raffaele Scientific Institute, 20132 Milan, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Vaghi
authors.forename: Roberta
authors.initials: R
authors.lastname: Pennucci
authors.forename: Francesca
authors.initials: F
authors.lastname: Talpo
authors.forename: Sara
authors.initials: S
authors.lastname: Corbetta
authors.forename: Valentina
authors.initials: V
authors.lastname: Montinaro
authors.forename: Cinzia
authors.initials: C
authors.lastname: Barone
authors.forename: Laura
authors.initials: L
authors.lastname: Croci
authors.forename: Paolo
authors.initials: P
authors.lastname: Spaiardi
authors.forename: G Giacomo
authors.initials: GG
authors.lastname: Consalez
authors.forename: Gerardo
authors.initials: G
authors.lastname: Biella
authors.forename: Ivan
authors.initials: I
authors.lastname: de Curtis
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001640:Bicuculline / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D002540:Cerebral Cortex / Q000166:cytology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D059330:GABAergic Neurons / Q000187:drug effects / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D006624:Hippocampus / Q000166:cytology*; D053444:Inhibitory Postsynaptic Potentials / Q000235:genetics; D007395:Interneurons / Q000187:drug effects / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D010879:Piperazines / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D050495:Vesicular Inhibitory Amino Acid Transport Proteins / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D018691:Excitatory Amino Acid Antagonists; D058787:GABA-A Receptor Antagonists; D010879:Piperazines; D026902:Potassium Channel Blockers; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; C492244:Viaat protein, mouse; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; D015761:4-Aminopyridine; C498771:Rac3 protein, mouse; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein; D001640:Bicuculline