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Identifier |
000460577 |
Title |
Morphological and functional characterization of cortical interneurons in Transgenic mice |
Alternative Title |
Μορφολογικός και λειτουργικός χαρακτηρισμός ενδονευρώνων του εγκεφαλικού φλοιού σε διαγωνιδιακούς μύες |
Author
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Σηφάκης, Ιάσων
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Thesis advisor
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Καραγωγέως, Δόμνα
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Reviewer
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Βιδάκη, Μαρία
Σιδηροπούλου, Κική
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Abstract |
Cortical interneurons (CINs), despite constituting a minority of cortical neurons, play
critical roles in cortical function and have been implicated in neurological disorders. CINs exhibit
remarkable diversity in morphology, molecular markers, and function, reflecting the complexity
of their development. This thesis explores the role of the small GTPase Rac1 in the maturation
of CINs, with a specific focus on somatostatin-expressing (SST+) CINs and the role of
TAG-1/CNTC-2 in the myelination of SST+ CINs and their functions.
Using a genetically engineered mouse model with Rac1 selectively ablated in medial
ganglionic eminence (MGE)-derived CINs, we investigated the morphological changes during
early postnatal development. Notably, we observed a significant reduction in the soma perimeter
of SST+ CINs, suggesting a role for Rac1 in cytoskeletal dynamics. Additionally, we assessed
synapse formation in these CINs. Immunocytochemistry revealed a decrease in both inhibitory
and excitatory synapse density on the soma and primary dendrites of SST+ CINs lacking Rac1.
Given the extensive connections between pyramidal cells and SST+ interneurons, we
propose further investigations into potential alterations in synapses on pyramidal cells in
Rac1-deficient mice. While Rac1's involvement in CIN development is well-documented, its
precise role in modulating the morphology and synaptogenesis of SST+ CINs during early
postnatal stages adds a new layer of complexity. Potential downstream molecules and
differential effects in distinct neuronal populations warrant further exploration.
Regarding the TAG-1/CNTC-2 mouse line, electrophysiological recordings show altered
potentiation of the CA1 circuit, where our findings reveal a stark difference between
TAG-1/CNTN-2 knockout and wild-type animals, suggesting the involvement of intricate
inhibitory-excitatory interactions and potential variations in NMDA receptor function.
This thesis offers a comprehensive journey into the world of CINs, unraveling their
complex development and functional significance. The insights gained not only expand our
understanding of neural circuitry but also open avenues for further exploration into the molecular
mechanisms that underlie cortical function.
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Language |
English |
Subject |
Morphology |
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Synapses |
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Ενδονευρώνες |
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Μορφολογία |
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Συνάψεις |
Issue date |
2023-12-08 |
Collection
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School/Department--School of Medicine--Department of Medicine--Post-graduate theses
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Type of Work--Post-graduate theses
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Permanent Link |
https://elocus.lib.uoc.gr//dlib/e/9/2/metadata-dlib-1700823748-874419-22944.tkl
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Views |
1061 |