Dokument: Spontaneous Na+ fluctuations in the neonatal mouse brain
| Titel: | Spontaneous Na+ fluctuations in the neonatal mouse brain | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=55739 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20210406-095806-3 | |||||||
| Kollektion: | Dissertationen | |||||||
| Sprache: | Englisch | |||||||
| Dokumententyp: | Wissenschaftliche Abschlussarbeiten » Dissertation | |||||||
| Medientyp: | Text | |||||||
| Autor: | Felix, Lisa [Autor] | |||||||
| Dateien: |
| |||||||
| Beitragende: | Prof. Dr. Christine R. Rose [Gutachter] Prof. Dr. Gottmann, Kurt [Gutachter] | |||||||
| Dewey Dezimal-Klassifikation: | 500 Naturwissenschaften und Mathematik » 570 Biowissenschaften; Biologie | |||||||
| Beschreibung: | Patterns of spontaneous activity are present across almost all structures within the neonatal brain, and are critical for the development of all cell types. In this environment, as in mature tissue, Na+ drives a multitude of membrane mechanisms in both neurons and astrocytes, and has an impact on several intracellular processes. Here, high levels of synchronous activity in neonatal structures are coupled with underdeveloped transmitter uptake systems and low expression levels of the primary Na+ extruder, the NKA. Taken together, these factors make it likely that cells undergo significant changes in their intracellular [Na+] during this time.
Using the Na+ specific fluorescent dye, SBFI, with in situ wide-field imaging in the mouse brain, I showed in this work for the first time, that a sub-set of both astrocytes and neurons undergo developmentally regulated spontaneous changes in [Na+]i to similar degrees in the cortex and hippocampus. The fluctuations were long lasting (~8 min), irregular in form and a-synchronous between cells. Going forward the study focused on the hippocampus, and a broad pharmacological approach showed that the changes did not appear to be directly linked to spontaneous network oscillations in Ca2+, which have been well described in neonatal neurons. The results indicate that hippocampal neuronal Na+ fluctuations (seen in ~20% of measured cells) are based on the voltage-gated Na+ channel dependent action potential firing, and consequent release of GABA from interneurons. This was confirmed by a model simulating neonatal interactions between interneurons and pyramidal cells, which was able to replicate the type of fluctuations seen in experimental measurements. In addition to neurons, around 40% of measured astrocytes showed spontaneous fluctuations in their [Na+]i. These were reduced in amplitude via blocking of action potential firing, however, many of the classical transmitters were ruled out as providing the driving force behind the fluctuations generation. Due to the number of cellular processes linked to Na+, and the extended nature of the elevation, we believe that the fluctuations are involved in regulating developmental processes such as migration and differentiation. | |||||||
| Lizenz: |  Urheberrechtsschutz | |||||||
| Fachbereich / Einrichtung: | Mathematisch- Naturwissenschaftliche Fakultät » WE Biologie » Neurobiologie | |||||||
| Dokument erstellt am: | 06.04.2021 | |||||||
| Dateien geändert am: | 06.04.2021 | |||||||
| Promotionsantrag am: | 31.10.2020 | |||||||
| Datum der Promotion: | 26.02.2021 |
