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 two-photon imaging of excitatory and inhibitory neuronal activity throughout the brain 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.

Chronic intracranial recordings after resection for epilepsy reveal a "running down" of epileptiform activity

“…Thus, it is unclear whether our findings should be reflective of ictal time parameters. Additionally, whether seizures are related to increased inhibitory activity or excitatory activity is not clear 14–18 . The balance may be different depending on whether the recording is from the seizure initiation zone or the propagation zone and when the recording is done relative to the timing of the seizure occurrence 19 .…”

“…Additionally, whether seizures are related to increased inhibitory activity or excitatory activity is not clear. [14][15][16][17][18] The balance may be different depending on whether the recording is from the seizure initiation zone or the propagation zone and when the recording is done relative to the timing of the seizure occurrence. 19 In one other case report of a child with focal epilepsy due to focal cortical dysplasia type II undergoing magnetoencephalography, the authors derived the aperiodic component of the spectrum preictally and during a seizure.…”

Seizure Event Detection Using Intravital Two-Photon Calcium Imaging Data

“…29, 30 Niemeyer et al used a clever method for detection of events by first finding global seizure events in the calcium data using a threshold detection in the mean trace and then generated a seed from a global signal and anchoring it to a point of recruitment, being the elbow of trace, or rather the maximum second derivative. 31…”

Aquatic Freshwater Vertebrate Models of Epilepsy Pathology: Past Discoveries and Future Directions for Therapeutic Discovery

“…A major advantage of zebrafish larva and Xenopus tadpoles is the ability to visualize the nervous system during seizure activity in real time. Using calcium imaging, scientists can look at both excitatory and inhibitory activity throughout the brain, identify areas of high activity, and assess the rate of spread of the seizure to other parts of the brain [ 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 ]. Calcium imaging can be combined with a variety of electrophysiological approaches to get a direct correlation between neuronal activity and electrical field potential [ 92 , 93 , 94 , 95 ].…”