Investigating acute microglia response to seizure activity in vivo: Combining 2-Photon imaging and EEG recording
Murmann JS. 2024. Investigating acute microglia response to seizure activity in vivo: Combining 2-Photon imaging and EEG recording. Institute of Science and Technology Austria.
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Thesis
| MS
| Published
| English
Author
Supervisor
Corresponding author has ISTA affiliation
Department
Series Title
ISTA Master's Thesis
Abstract
Epilepsy affects about 50 to 65 million people globally. It summarizes a spectrum of neurological
disorders that have in common a hyperactivity of the neuronal network resulting in seizures. A common
assumption is that an imbalance between neuronal excitation and inhibition is a key mechanism in
seizure generation and epileptogeneisis. In at least one-third of the patients, current therapies have
proven unsuccessful in treating seizure progression. One potential reason could be that the therapies
only focus on neurons. Recent studies suggest that neuronal hyperactivity causes a microglial
response, which reinstates brain homeostasis. Additionally, interactions between microglia and neurons
have been shown to inhibit neuronal firing and dampen seizure activity. However, the exact relationship
between microglia and seizure progression in epilepsy is yet to be elucidated. A main bottleneck is that
several studies investigate microglia dynamics in ex vivo slice models, which can severely affect the
microglia dynamics due to their rapid response to environmental changes. On the other hand, in vivo
studies focus mostly on behavior characterization of the epileptic seizure phenotype and their long-term
consequences on microglia activity leaving out the direct consequences of acute seizure activity on
microglia dynamics.
Here, we perform a pilot study to combine electroencephalography (EEG) and in vivo live imaging to
directly monitor and correlate the onset of seizure activity with microglia response. To induce seizures,
we take advantage of the kainic acid (KA) model, which represents similar neuropathological and
electroencephalographic features seen in human patients with temporal lobe epilepsy (TLE). After
confirmation of induction of the seizure and microglia activity in the hippocampus as a focal point, we
investigated whether these changes also reached the primary visual cortex (V1) as a secondary
generalized seizure activity. Indeed, we found that microglia changed their morphology at high doses
of KA in the V1. Next, we optimized each of the two methodological components: for the EEG recording,
our initial attempts under the microscope suffered from extensive electrical noise, which overlaid the
actual signal. Thus, we built a customized Faraday-cage and confirmed that the signal-to-noise ratio
was sufficiently reduced to be able to record brain oscillatory activity. For the in vivo live imaging of
microglia, we had to optimize the imaging parameters, so that we would be able to detect microglial
processes in a sufficient resolution to track their process changes. Finally, we combined both
methodologies with the KA model. We confirmed that KA induced seizure activity and found first
indication that those correlate with microglia volume changes.
Overall, we have developed a first methodological approach, which allows the analysis of the acute
effects of seizure onset on microglia. Future studies will have to continue to optimize the drift during
imaging recording and the post-image analysis.
Publishing Year
Date Published
2024-05-02
Publisher
Institute of Science and Technology Austria
Acknowledged SSUs
Page
54
ISSN
IST-REx-ID
Cite this
Murmann JS. Investigating acute microglia response to seizure activity in vivo: Combining 2-Photon imaging and EEG recording. 2024. doi:10.15479/at:ista:15352
Murmann, J. S. (2024). Investigating acute microglia response to seizure activity in vivo: Combining 2-Photon imaging and EEG recording. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:15352
Murmann, Julie Stefanie. “Investigating Acute Microglia Response to Seizure Activity in Vivo: Combining 2-Photon Imaging and EEG Recording.” Institute of Science and Technology Austria, 2024. https://doi.org/10.15479/at:ista:15352.
J. S. Murmann, “Investigating acute microglia response to seizure activity in vivo: Combining 2-Photon imaging and EEG recording,” Institute of Science and Technology Austria, 2024.
Murmann JS. 2024. Investigating acute microglia response to seizure activity in vivo: Combining 2-Photon imaging and EEG recording. Institute of Science and Technology Austria.
Murmann, Julie Stefanie. Investigating Acute Microglia Response to Seizure Activity in Vivo: Combining 2-Photon Imaging and EEG Recording. Institute of Science and Technology Austria, 2024, doi:10.15479/at:ista:15352.
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