PUBLICATION

Calcium imaging and dynamic causal modelling reveal brain-wide changes in effective connectivity and synaptic dynamics during epileptic seizures

Authors
Rosch, R.E., Hunter, P.R., Baldeweg, T., Friston, K.J., Meyer, M.P.
ID
ZDB-PUB-180824-11
Date
2018
Source
PLoS Computational Biology   14: e1006375 (Journal)
Registered Authors
Hunter, Paul, Meyer, Martin
Keywords
none
MeSH Terms
  • Animals
  • Bayes Theorem
  • Brain/physiopathology
  • Calcium/metabolism*
  • Connectome/methods*
  • Electroencephalography
  • Epilepsy/physiopathology
  • Larva/metabolism
  • Models, Neurological
  • Nerve Net/physiology
  • Neurons/physiology
  • Seizures/chemically induced
  • Seizures/physiopathology*
  • Synaptic Transmission/physiology
  • Zebrafish/embryology
PubMed
30138336 Full text @ PLoS Comput. Biol.
Abstract
Pathophysiological explanations of epilepsy typically focus on either the micro/mesoscale (e.g. excitation-inhibition imbalance), or on the macroscale (e.g. network architecture). Linking abnormalities across spatial scales remains difficult, partly because of technical limitations in measuring neuronal signatures concurrently at the scales involved. Here we use light sheet imaging of the larval zebrafish brain during acute epileptic seizure induced with pentylenetetrazole. Spectral changes of spontaneous neuronal activity during the seizure are then modelled using neural mass models, allowing Bayesian inference on changes in effective network connectivity and their underlying synaptic dynamics. This dynamic causal modelling of seizures in the zebrafish brain reveals concurrent changes in synaptic coupling at macro- and mesoscale. Fluctuations of both synaptic connection strength and their temporal dynamics are required to explain observed seizure patterns. These findings highlight distinct changes in local (intrinsic) and long-range (extrinsic) synaptic transmission dynamics as a possible seizure pathomechanism and illustrate how our Bayesian model inversion approach can be used to link existing neural mass models of seizure activity and novel experimental methods.
Genes / Markers
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Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping