Modelling Epilepsy in Zebrafish
Zebrafish have recently emerged as an important animal model of epilepsy: some of the same mutations that cause epilepsy in patients can also cause epilepsy in zebrafish; we can use molecular genetic tools to interrogate cellular mechanisms of disease; and we can now record whole-brain images of brain function at single-cell resolution.
For this research stream, we are using light-sheet microscopy in zebrafish with epilepsy-causing mutations. This allows us to record activity during and between seizures and try and reconstruct the functional connections between different brain areas and even different groups of neurons.
Using a range of state-of-the-art tools from network neuroscience, we will relate the abnormal neuronal dynamics introduced by the mutations to the sort of EEG dynamic abnormalities we see in patients with corresponding epilepsies. This work aims to relate this novel powerful animal model to our knowledge of epilepsy in patients to try and develop new strategies of how seizures could be controlled.
This paper illustrates how computational modelling can be applied can be used to explain the brain-wide changes that occur during epileptic seizures.
Rosch et al. (2017) bioRxiv: 10.1101/160259
This code applies dynamic causal modelling to brain-wide calcium imaging in the larval zebrafish brain
Github: Zebrafish seizure modelling