Light sheet calcium imaging captures brain activity in zebrafish larvae

  • light sheet imaging allows optical sectioning and fast volumetric imaging for long-term recordings
  • when averaged by region, this yields spatially unbiased recording of distributed neuronal activity (unlike local field potentials)
  • calcium fluorescence dynamics allow us to reconstruct network connectivity between zebrafish brain regions
  • light sheet imaging reveals a baseline network architecture that contains the optic tectum as centrally connected hub

Seizures induced with PTZ cause network-wide activity changes

  • we induced seizures in 3 zebrafish larvae (5dpf, neuronal GCaMP6F) with the chemoconvulsant pentylenetetrazole (PTZ)
  • PTZ causes wide-spread synchronised bursts of activity, changing the spectral composition of activity across brain regions
  • a correlation matrix of power spectra across sliding time windows reveals transitions between seizure phases
  • PTZ-induced seizures unfold in distinct phases that can be tracked by spectral summaries of the calcium fluorescence singal

Bayesian model inversion estimates synaptic coupling parameters

  • applying a hierarchical dynamic causal modelling approach, we fitted biophysical network models to each time window
  • slow fluctuations in synaptic parameters are captured as between-window changes in DCM parameters
  • we compared families of models to identify which parameter types change during induced seizures
  • seizures are associated with faster neuronal responses overall and an inhibition/excitation imbalance characterised by relatively more overall excitation

Seizures follow trajectories in a reduced parameter space

  • we can summarise the changes of multiple parameters across the time windows with just two principal components
  • simulations help understand the contribution of different model parameters to the spectral feature in the neuronal output
  • intrinsic connectivity mainly effect power, whilst time constants shift frequency peaks
  • PTZ induces parameter changes associated with high frequency oscillations early in the experiment