Barth, Lydia. Stem cell derived neurons : physiology of early differentiation and development. 2015, PhD Thesis, University of Basel, Faculty of Science.
Restricted to Repository staff only until 31 October 2018.
Official URL: http://edoc.unibas.ch/diss/DissB_11512
In my thesis work I used such a culture system to compare the functional development of mES cell derived neurons from different genetic backgrounds. I spent a lot of time establishing experimental conditions to study these cells using electrophysiological techniques. I quantified several key parameters such as resting membrane potential, voltage-gated channel activity, appearance of action potentials, to describe the neuronal differentiation of the cells. In the first days after seeding the precursors possess an immature physiology, with high input resistances, few voltage-sensitive conductance and immature spiking patterns. During subsequent development an increasing amount of voltage gated sodium- and potassium currents appeared, leading to more and more mature spiking patterns. Mature neurons form synaptically connected networks containing excitatory and inhibitory neurons. We investigated the development of spontaneous excitatory- and inhibitory postsynaptic currents (sEPSCs and sIPSCs) in these cultures. We then built upon this knowledge of normal development to study mES cell-derived neurons defective in MeCP2 signaling. This genetic defect causes an important neurodevelopmental defect in mice and in humans. We were able to show that key features of the developmental defect – a disturbed maturation of inhibitory synapses – could be reproduced in our system. For further characterization of inhibitory interneurons we derived stem cells from a GAD67-GFP cell line under two pharmacological conditions as KCl and TTX which change the activity level up or down. This will aid to understand more about the developmental processes of neurons and will help finding functional deficits in neurodevelopmental diseases.
|Committee Members:||Reichert, Heinrich|
|Faculties and Departments:||05 Faculty of Science > Departement Biozentrum > Former Organization Units Biozentrum > Pharmacology/Neurobiology (Vogt)|
|Bibsysno:||Link to catalogue|
|Number of Pages:||82 Bl.|
|Last Modified:||30 Jun 2016 10:58|
|Deposited On:||07 Dec 2015 14:40|
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