Abstract
Fast and slow neural waves have been observed to propagate in the human brain during seizures. Yet the nature of these waves is difficult to study in a surgical setting. Here, we report an observation of two different traveling waves propagating in the in-vitro epileptic hippocampus at speeds similar to those in the human brain. A fast traveling spike and a slow moving wave were recorded simultaneously with a genetically encoded voltage sensitive fluorescent protein (VSFP Butterfly 1.2) and a high speed camera. The results of this study indicate that the fast traveling spike is NMDA-sensitive but the slow moving wave is not. Image analysis and model simulation demonstrate that the slow moving wave is moving slowly, generating the fast traveling spike and is, therefore, a moving source of the epileptiform activity. This slow moving wave is associated with a propagating neural calcium wave detected with calcium dye (OGB-1) but is independent of NMDA receptors, not related to ATP release, and much faster than those previously recorded potassium waves. Computer modeling suggests that the slow moving wave can propagate by the ephaptic effect like epileptiform activity. These findings provide an alternative explanation for slow propagation seizure wavefronts associated with fast propagating spikes.
Highlights
Seizures are known to propagate and the localization of the focus is essential to a successful therapeutic intervention
The fast traveling spikes refer to the 4-AP induced inter-ictal epileptiform activity propagating at a speed of approximately 0.1 m/s and previously observed in the unfolded hippocampus[5]
Most of the fast traveling waves originated in the temporal region of the longitudinal hippocampal slice indicating that the temporal area of the hippocampus is more epileptogenic that the septal side
Summary
By taking advantage of the state-of-the-art voltage-sensitive protein and calcium imaging methods, two different types of traveling waves were detected and traced in longitudinal hippocampal slices. Calcium imaging experiments reveal that a neural calcium wave was always accompanied by a fast propagating spike recorded electrically and was with similar speed and direction of propagation already reported in the previous study[6] Taken together, these data indicate that the slow propagating neuronal calcium wave is the moving source of the spikes. The fast traveling spikes appear to propagate first and are followed by the calcium wave in the voltage imaging experiments (Fig. 3e) but it should be noted that the fast traveling spikes were triggered by the initiation of the slow moving wave based on the model simulation. Our model simulation suggests that the slow traveling neural source is consistent with calcium spikes propagating by electrical field like epileptiform activity. The slow neural source could possibly explain the slow recruitment of seizures in the early stage or the multi-sites of epilepsy foci
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