Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.06.28.172460v1?rss=1 Authors: Petrucci, A. N., Joyal, K. G., Li, R., Chou, J. W., Vencer, K. M., Buchanan, G. F. Abstract: Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in patients with refractory epilepsy. A proposed risk marker for SUDEP is the duration of post-ictal generalized EEG suppression (PGES). The mechanisms underlying PGES are unknown. Serotonin (5-HT) has been implicated in SUDEP pathophysiology. Seizures suppress activity of 5-HT neurons in the dorsal raphe nucleus (DRN). We hypothesized that suppression of DRN 5-HT neuron activity contributes to PGES and increasing 5-HT neurotransmission or stimulating the DRN before a seizure would decrease PGES duration. Adult C57BL/6 and Pet1-Cre mice received EEG/EMG electrodes, a bipolar stimulating/recording electrode in the right basolateral amygdala, and either a microdialysis guide cannula or an injection of adeno-associated virus (AAV) allowing expression of channelrhodopsin2 plus an optic fiber into the DRN. Systemic application of the selective 5-HT reuptake inhibitor citalopram (20 mg/kg) decreased PGES duration from seizures induced during wake (n = 23) and NREM sleep (n = 13) whereas fluoxetine (20 mg/kg) pretreatment decreased PGES duration following seizures induced from wake (n = 11), but not NREM sleep (n = 9). Focal chemical (n = 6) or optogenetic (n = 8) stimulation of the DRN reduced PGES duration following kindled seizures and reduced morality following maximal electroshock seizures (n = 6) induced during wake. During PGES, animals exhibited immobility and suppression of EEG activity that was reduced by citalopram pretreatment. These results indicate that 5-HT and the DRN may regulate PGES and seizure-induced mortality. Copy rights belong to original authors. Visit the link for more info