Epileptic seizures lead to a loss of near-critical brain organisation in the zebrafish brain
Abstract number :
231
Submission category :
1. Basic Mechanisms / 1E. Models
Year :
2020
Submission ID :
2422577
Source :
www.aesnet.org
Presentation date :
12/6/2020 12:00:00 PM
Published date :
Nov 21, 2020, 02:24 AM
Authors :
Dominic Burrows, King's College London; Mark Richardson - King's College London; Danielle Bassett - University of Pennsylvania; Martin Meyer - King's College London; Richard Rosch - King's College London;;
Rationale:
Zebrafish have emerged as an important new model for epilepsy. Recent advances in microscopy now allow fast whole-brain functional calcium imaging at single-cell resolution, including during epileptic seizures. In line with a variety of other model systems, neuronal avalanches in the zebrafish brain exhibit scale invariance suggestive of criticality, from which the brain may deviate during epileptic seizures. How do entire brain networks constrain avalanche cascades to support a loss of near-critical dynamics during seizures?
Method:
We perform in vivo 2-photon imaging of GCaMP6s larval zebrafish (n=10), at single cell resolution across the whole brain, during pentylenetrazole (PTZ) induced seizures.
Results
We find that during epileptic seizures, avalanche distributions significantly deviate from baseline power-laws with a decrease in exponent. Interestingly, we find that this deviation from baseline avalanche dynamics is conserved across scales and data modalities, also occurring in human seizures (EEG). Furthermore seizure state transitions are characterised by a loss of power-law distributions in eigenspectrum and functional connectivity-distance profiles, and an increase in branching ratio. Our findings indicate that the zebrafish brain deviates from near-critical organisation during epileptic seizures. Because of the spatial resolution this model system affords, we then link avalanche statistics to mesoscale topological features that support longer avalanches. Using network modelling we demonstrate that an increased occurrence of cycle density, edge density and a loss of small-worldness explain seizure avalanche dynamics.
Conclusion:
This data suggests that epileptic seizures may emerge as a loss of near-critical organisation, supported by the emergence of several network motifs. More generally this work illustrates how advanced imaging in zebrafish models of epilepsy may support a more in-depth understanding of multi-scale dynamics of epileptic seizures.
Funding:
:DR Burrows is funded by the Medical Research Council and the Sackler Institute for Translational Neurodevelopment
M Meyer is funded by the Wellcome Trust
R Rosch is funded by the Wellcome Trust
Basic Mechanisms