Seizures initiate in zones of relative hyperexcitation in a zebrafish epilepsy model

Abstract

Seizures are thought to arise from an imbalance of excitatory and inhibitory neuronal activity. While most classical studies suggest excessive excitatory neural activity plays a generative role, some recent findings challenge this view and instead argue that excessive activity in inhibitory neurons initiates seizures. We investigated this question of imbalance in a zebrafish seizure model with multi-regional two-photon imaging of excitatory and inhibitory neuronal activity using a nuclear-localized calcium sensor. We found that seizures consistently initiated in circumscribed zones of the midbrain before propagating to other brain regions. Excitatory neurons were both more prevalent and more likely to be recruited than inhibitory neurons in initiation as compared with propagation zones. These findings support a mechanistic picture whereby seizures initiate in a region of hyper-excitation, then propagate more broadly once inhibitory restraint in the surround is overcome.

Efficacy of Tricaine (MS-222) and Hypothermia as Anesthetic Agents for Blocking Sensorimotor Responses in Larval Zebrafish

“…The videos were first filtered using a two-dimensional Gaussian filter (σ = 2) (Matlab: imgaussfit ). Individual pixels were then smoothed using a Butterworth filter (1st order, cut-off frequency 0.2 Hz; Matlab: butter ), as described by Niemeyer et al ( 30 ). Individual pixels were correlated with the median fluorescence trace in order to generate a pixel correlation mask, only pixels with a correlation >0.5 were included in this mask.…”