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Identifier 000444055
Title Morphological and synaptic properties of Rac1 mutant postnatal cortical interneurons
Alternative Title Μορφολογικές και συναπτικές ιδιότητες διάμεσων νευρώνων του φλοιού μυών, ελλειμματικών ως προς τη μικρή GTPάση Rac1, μετά τη γέννηση
Author Παπαδάκη, Αριάδνη
Thesis advisor Καραγωγέως, Δόμνα
Reviewer Βιδάκη, Μαρίνα
Σιδηροπούλου, Κυριακή
Abstract GABAergic cortical interneurons (CINs) represent only ~20% of all cortical neurons, yet they are crucial factors in proper cortical function and have been implicated in severe neuropsychiatric disorders. These cells are characterized by a remarkable morphological, molecular and functional diversity. Based on the expression of specific markers, we can classify them into two main subclasses; Parvalbumin (PV) and Somatostatin (SST) CINs. Despite the progress in unravelling many aspects CIN development, most studies have identified extracellular signals rather than intracellular components mediating the response to the former. In brief, developmental phases of CINs include neurogenesis, migration, morphogenesis and synaptogenesis, programmed cell death and circuit refinement. Interestingly, emerging evidence implicates Rac1, a small GTPase, in CIN development. To name a few, ablation of Rac1 specifically from MGE-derived cells (PV and SST CINs), via Cre/loxP technology, results in a profound reduction of CIN migration to the cerebral cortex, impaired synaptic plasticity and disorganized oscillatory activity. However, we are still lacking information on the role of Rac1 in early maturation of CINs, when morphological development and synaptogenesis occur. Therefore, our aim was to examine the role of Rac1 in the morphological and synaptic properties of CINs during early postnatal period. To this end, we prepared primary mixed cortical cultures from Rac1cKO and control mice. We demonstrate that ablation of Rac1 significantly reduces soma size and complexity of PV CINs. Additionally, Rac1 deficient PV CINs have significantly fewer inhibitory synapses on their soma and primary dendrites, whereas excitatory synapse density was significantly increased on their primary dendrites. Hence, our analysis strongly supports that Rac1 is an essential molecule for the proper maturation of, at least PV, CINs, in terms of morphogenesis and synapse formation. Our data will hopefully contribute to our understanding of CIN dysfunction, often observed in animal models and clinical studies.
Language English
Issue date 2021-12-01
Collection   School/Department--School of Medicine--Department of Medicine--Post-graduate theses
  Type of Work--Post-graduate theses
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