Generalized neuronal activity in gabra1−/− following light exposure and sudden death following generalized seizures. A, Gabra1+/− and NeuroD:GCaMP6f +/− were intercrossed, and neuronal activity was monitored under a confocal microscope at 8 days postfertilization. After a period of 30 minutes in complete darkness, switching on the laser induced a broad neuronal activity in both optic tecta in gabra1−/− (n = 12) compared to gabra1+/+ siblings (n = 10) that lasted for few seconds (arrows). The intense neuronal activity of −/− larvae was rescued to wild‐type (WT) level after exposure to valproic acid (VPA; 50 μmol/L, n = 7). B, Fluorescence quantification in the optic tecta before and after laser exposure shows a significant increase of fluorescence in −/− larvae compared to +/+ siblings. Each point corresponds to the relative quantification of fluorescence from a frame with 400‐millisecond exposure. VPA treatment fully rescues the fluorescence back to the WT level (Student t test: *P < 0.05, ** P < 0.01, ***P < 0.005). C, The whirlpool onset (ie, clonic‐like phase) increased with age, with a full penetrance at 6 weeks postfertilization (wpf) onward. D, Sudden unexpected death in epilepsy (SUDEP) events were quantified and occurred from 4 wpf onward only in gabra1−/− mutants. Of note is that data shown here correspond to the actual SUDEP events witnessed, but it is very likely that it occurs in many more fish
|