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Identifier

000452166

Title

Functional and morphological properties of postnatal Rac1, Rac3 and Rac1/Rac3 deficient cortical interneurons

Alternative Title

Λειτουργικές και μορφολογικές ιδιότητες των μεταγεννητικών ενδονευρώνων απουσία της Rac1, Rac3 ή των Rac1/Rac3

Author

Πέππα, Στυλιανή Κ.

Thesis advisor

Καραγωγέως, Δόμνα

Reviewer

Σιδηροπούλου, Κυριακή
Βιδάκη, Μαρίνα

Abstract

GABAergic cortical interneurons (CINs) are a subcategory of cortical neurons that comprise a small percentage of the cortical neurons. However, they play a crucial role in proper cortical function and have been implicated in severe neuropsychiatric and neurodegenerative disorders. CINs are a diverse group of neurons with different molecular, morphological and functional characteristics. They are divided in subclasses depending on their features. A key selection criterion is the expression of specific markers. They are classified into two main groups according to the expression of either the protein parvalbumin (PV), or the neuropeptide somatostatin (SST). It has been suggested that cortical interneurons participate in migration, morphogenesis and circuit refinement. The development of the cortical interneurons is mediated by both external and internal signals. Regarding the intracellular proteins involved, one component that has been studied to some extent is Rac1 that is a member of the Rho-GTPases family. Rac1 is co-expressed with Rac3, which belongs to the same protein family, in developing neurons. According to studies deletion of Rac1 specifically from MGE-derived interneurons led to decreased cell cycle exit and as a result there is a 50% decrease in the cortical interneurons that manage to reach the cortex. Furthermore, when Rac1 deletion was combined with Rac3 ablation led to a significant loss of CINs, surmounting to 80% absence of these cells from the cortex and only 20% of cortical interneurons manage to migrate to the cortex. Our aim was to examine the role of Rac1 on the morphology of CINs by examining the morphological properties of the Rac1 mutant CINs in vivo, in the postnatal cortex given that these cells have migrated to an environment with decreased inhibition. Along with that, we wanted to explore how the concurrent absence of Rac1 and Rac3 affects the spine formation of cortical neurons. Last but not least, our objective was to elucidate whether ablation of Rac1 affects other genes that are involved in the cell cycle. To this end, we injected a Cre-dependent fluophore-expressing adeno-associated virus in control and Rac1 mutant mice. We demonstrate that ablation of Rac1 significantly increases the branch complexity of CINs and at the same time it does not affect soma size. In addition, the simultaneous deletion of Rac1 and Rac3 leads pyramidal cells to form more spines and it increases their density as well. Besides that, down-regulation of cell cycle related genes was confirmed when Rac1 was ablated. Hence, our analysis strongly supports that Rac1 plays a pivotal role regarding the interneuron morphology as well as the cell cycle. At the same time the combined expression of Rac1 and Rac3 allows the cells to form functional spines.

Language

English

Subject

Functionality

Morphology

Ενδονευρώνες

Λειτουργικότητα

Μορφολογία

Issue date

2022-11-25

Collection

School/Department--School of Sciences and Engineering--Department of Biology--Post-graduate theses