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.

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Maximum entropy modelling in the larval zebrafish brain [paper]

We use calcium imaging data in zebrafish larvae, giving us access to the activity of single neurons across the whole brain. In this dataset, fitting a pairwise maximum entropy model allows us to reproduce activity patterns and transitions between them.

Rosch et al. (2024) Phys Rev X https://doi.org/10.1103/PhysRevX.14.031050

Spontaneous brain activity emerges from pairwise interactions in the larval zebrafish brain [preprint]

Brain activity emerges from neuron-to-neuron interactions. Here we use maximum entropy modelling to explain whole-brain patterns of brain activity in larval zebrafish.

Rosch et al. (2023) arXiv:
https://doi.org/10.48550/arXiv.2309.05939

Microscale neuronal activity collectively drives chaotic and inflexible dynamics at the macroscale in seiuzres [paper]

This publication interrogates the effects of microscale changes in neuronal dynamics on macroscale emergent dynamics in epileptic seizures.

Burrows et al. J Neurosci (2023): doi.org/10.1523/JNEUROSCI.0171-22.2023

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In this manuscript we identify key changes in neuronal dynamics that unfold at single-cell scale in the seizing larval zebrafish brain

Burrows et al. bioRxiv (2021): doi.org/10.1101/2021.10.14.464473

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In this review we summarise the state of Calcium imaging in larval zebrafish models of epilepsy and its theoretical foundations.

Burrows et al. (2020) Eur J Paed Neurol: 10.1016/j.ejpn.2020.01.006

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Here we discuss the implications of a very interesting zebrafish paper form researchers in Norway, investigating glial-cell contributions to seizure dynamics

Rosch & Dulla (2020) Epilepsy Curr: 10.1177/1535759720906115

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A Novel zebrafish model of GABRG2-associated epilepsy [paper]

Lead by a team of collaborators at the University of Montreal, here we describe a new model of a human genetic epilepsy in zebrafish.

Liao et al (2019) Dis Model Mechan: 10.1242/dmm.040782

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DCM of calcium imaging in zebrafish seizures [PLoS CB]

The paper below is now out in its full version, and was on the ‘virtual cover’ of PLoS Computational Biology

Rosch et al (2018) PLoS Comp Biol: 10.1371/journal.pcbi.1006375

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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

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This code applies dynamic causal modelling to brain-wide calcium imaging in the larval zebrafish brain

Github: Zebrafish seizure modelling