Optogenetic activation of 5-HT neurons in the dorsal raphe suppresses seizure-induced respiratory arrest and produces anticonvulsant effect in the DBA/1 mouse SUDEP model.

摘要: Sudden unexpected death in epilepsy (SUDEP) is a devastating complication. Seizure-induced respiratory arrest (S-IRA) occurs many witnessed SUDEP patients and animal models as an initiating event leading to death. Thus, understanding the mechanisms underlying S-IRA will advance development of preventive strategies against SUDEP. Serotonin (5-HT) important modulator for vital functions, including respiration arousal, deficiency 5-HT signaling strongly implicated models, DBA/1 mouse. However, brain structures that contribute remain elusive. We hypothesized dorsal raphe (DR), which sends projections forebrain, S-IRA. The present study used optogenetics mouse model selectively activate neurons DR. Photostimulation DR significantly reversibly reduced incidence evoked by acoustic stimulation. Activation suppressed tonic seizures most mice without altering seizure latency duration wild running clonic This suppressant effect photostimulation on independent optogenetic stimulation also induced pentylenetetrazole, proconvulsant widely human generalized seizures. S-IRA-suppressing was increased 5-hydroxytryptophan, chemical precursor synthesis, reversed ondansetron, specific 5-HT3 receptor antagonist, indicating reduction specifically mediated enhanced neurotransmission. Our findings suggest deficits neurotransmission are mice, targeted intervention potentially useful prevention