Optogenetic stimulation of the dorsal raphe nucleus (DRN) reduced PGES following seizures in amygdala kindled mice. (A, B) Duration of PGES (A) and seizures (B) following laser stimulation (blue; 473 nm; 4 Hz, 10 mW, 2% duty; 10 s on / 10 s off) or no stimulation (black) in DRN neurons prior to seizure induction during wake in Pet1-Cre (n = 7) and WT (n = 8) mice injected with AAV-ChR2 into the DRN. *, p < 0.05. (C) Depiction of optic fiber positioning within the DRN in Pet1-Cre mice injected with AAV-ChR2. Aq, aqueduct; DRN, dorsal raphe nucleus; MLF, medial longitudinal fasciculus; PAG, periaqueductal gray. (D,E) Immunostained coronal section depicting optical fiber tracts (long solid arrow), ChR2 expression (red), serotonergic (5-HT) cell bodies (green/non-solid small arrow), and co-expression (yellow/solid small arrows) within the DRN of a Pet1-Cre (D) and WT (E) mouse that received an injection of AAV-ChR2 into DRN. Box indicates location of magnified cells on right (top, 5-HT cells; middle, ChR2; bottom, merge). Aq, aqueduct; MLF, medial longitudinal fasciculus; PAG, periaqueductal gray. Scale bar: 500 μm, 50 μm. (F) Representative spectral plots of PGES duration following either no laser (left) or laser stimulation (right) of DRN 5-HT neurons prior to seizure induction in a Pet1-Cre mouse injected with AAV-ChR2.