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Loss of either Rac1 or Rac3 GTPase differentially affects the behavior of mutant mice and the development of functional GABAergic networks
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Pennucci, Roberta, Talpo, Francesca, Astro, Veronica, Montinaro, Valentina, More, Lorenzo, Cursi, Marco, Castoldi, Valerio, Chiaretti, Sara, Bianchi, Veronica, Marenna, Silvia, Cambiaghi, Marco, Tonoli, Diletta, Leocani, Letizia, Biella, Gerardo, D'Adamo, Patrizia and de Curtis, Ivan (2015) Loss of either Rac1 or Rac3 GTPase differentially affects the behavior of mutant mice and the development of functional GABAergic networks. Cerebral Cortex . pp. 1-18. doi:10.1093/cercor/bhv274
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WRAP_Cereb. Cortex-2015-Pennucci-cercor-bhv274.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons: Attribution-Noncommercial 4.0. Download (1833Kb) | Preview |
Official URL: http://dx.doi.org/10.1093/cercor/bhv274
Abstract
Rac GTPases regulate the development of cortical/hippocampal GABAergic interneurons by affecting the early development and migration of GABAergic precursors. We have addressed the function of Rac1 and Rac3 proteins during the late maturation of hippocampal interneurons. We observed specific phenotypic differences between conditional Rac1 and full Rac3 knockout mice. Rac1 deletion caused greater generalized hyperactivity and cognitive impairment compared with Rac3 deletion. This phenotype matched with a more evident functional impairment of the inhibitory circuits in Rac1 mutants, showing higher excitability and reduced spontaneous inhibitory currents in the CA hippocampal pyramidal neurons. Morphological analysis confirmed a differential modification of the inhibitory circuits: deletion of either Rac caused a similar reduction of parvalbumin-positive inhibitory terminals in the pyramidal layer. Intriguingly, cannabinoid receptor-1-positive terminals were strongly increased only in the CA1 of Rac1-depleted mice. This increase may underlie the stronger electrophysiological defects in this mutant. Accordingly, incubation with an antagonist for cannabinoid receptors partially rescued the reduction of spontaneous inhibitory currents in the pyramidal cells of Rac1 mutants. Our results show that Rac1 and Rac3 have independent roles in the formation of GABAergic circuits, as highlighted by the differential effects of their deletion on the late maturation of specific populations of interneurons.
| Item Type: | Journal Article | ||||
|---|---|---|---|---|---|
| Subjects: | R Medicine > RJ Pediatrics | ||||
| Divisions: | Faculty of Science > Life Sciences (2010- ) | ||||
| Library of Congress Subject Headings (LCSH): | Telethon | ||||
| Journal or Publication Title: | Cerebral Cortex | ||||
| Publisher: | Oxford University Press | ||||
| ISSN: | 1047-3211 | ||||
| Official Date: | 17 November 2015 | ||||
| Dates: |
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| Number of Pages: | 18 | ||||
| Page Range: | pp. 1-18 | ||||
| DOI: | 10.1093/cercor/bhv274 | ||||
| Status: | Peer Reviewed | ||||
| Publication Status: | Published | ||||
| Access rights to Published version: | Restricted or Subscription Access | ||||
| Funder: | Telethon |
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