Public Defence: Cecilie Bugge Bakketun

Due to copyright issues, an electronic copy of the thesis must be ordered from the faculty. For the faculty to have time to process the order, the order must be received by the faculty at the latest 2 days before the public defence. Orders received later than 2 days before the defence will not be processed. After the public defence, please address any inquiries regarding the thesis to the candidate.

Trial Lecture – time and place

See Trial Lecture.

Adjudication committee

• First opponent: Professor Nanna MacAulay, University of Copenhagen, Denmark,
• Second opponent: Senior Consultant Eli Gunnarson, Karolinska University Hospital and Karolinska Institutet, Sweden,
• Third member and chair of the evaluation committee: Associate Professor Jørgen Afseth Sugar, University of Oslo

Chair of the Defence

Associate Professor Koen Vervaeke, University of Oslo

Principal Supervisor

Vidar Jensen, Senior Engineer, University of Oslo

Summary

The brain consists of many cell types in addition to neurons. Astrocytes (star cells) are often called the caretaker cells of the brain because they ensure a stable extracellular chemical environment. This is crucially important in order to allow precise neuronal signaling.

In my doctoral thesis Roles of Astrocytes in Extracellular Potassium and Glutamate Regulation we find that the water channel AQP4 in the astrocyte cell membrane affects how astrocytes handle K⁺ released by neurons during synaptic activity. We find that mice lacking AQP4 display higher extracellular K⁺ levels during synaptic stimulation than wild-type mice. Absence of AQP4 causes astrocytes to swell less when exposed to high K⁺ solutions. These are important findings because elevated K⁺ levels disrupt normal nerve signaling and are seen in a number of brain diseases including epilepsy. It is therefore essential to investigate how astrocytes perform their strict regulation of extracellular K⁺ levels.

Furthermore, our investigations suggest that astrocytes may play a protective role during epileptogenesis. By using a disease model of temporal lobe epilepsy, we find that mice with reduced astrocytic Ca²⁺ signaling suffer from more severe epileptic seizures and an increased mortality compared to control mice. Ca²⁺ signals are transient elevations in intracellular Ca²⁺ concentration used by astrocytes to communicate with each other and their surroundings. We also find that the level of the excitatory neurotransmitter glutamate fell in mice devoid of normal Ca²⁺ signals, which may indicate increased neuronal death and subsequently reduced glutamate release in these mice.

The studies in this thesis consist of electrophysiological experiments and two-photon laser microscopy on thin slices of living brain tissue from mice. The thesis sheds light on important aspects of astrocytic regulation of the extracellular environment in the healthy brain and in a disease model of temporal lobe epilepsy.

Additional information

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