Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in refractory epilepsy patients. Accumulating evidence from recent human studies and animal models suggests that seizure-related respiratory arrest may be important for initiating cardiorespiratory arrest and death. Prior evidence suggests that apnea onset can coincide with seizure spread to the amygdala and that stimulation of the amygdala can reliably induce apneas in epilepsy patients, potentially implicating amygdalar regions in seizure-related respiratory arrest and subsequent postictal hypoventilation and cardiorespiratory death. This study aimed to determine if an extended amygdalar structure, the dorsal bed nucleus of the stria terminalis (dBNST), is involved in seizure-induced respiratory arrest (S-IRA) and death using DBA/1 mice, a mouse strain which has audiogenic seizures (AGS) and a high incidence of postictal respiratory arrest and death. The presence of S-IRA significantly increased c-Fos expression in the dBNST of DBA/1 mice. Furthermore, disruption of synaptic output from the dBNST via viral-induced tetanus neurotoxin (TeNT) significantly improved survival following S-IRA in DBA/1 mice without affecting baseline breathing or hypercapnic (HCVR) and hypoxic ventilatory response (HVR). This disruption in the dBNST resulted in changes to the balance of excitatory/inhibitory (E/I) synaptic events in the downstream brainstem regions of the lateral parabrachial nucleus (PBN) and the periaqueductal gray (PAG). These findings suggest that the dBNST is a potential subcortical forebrain site necessary for the mediation of S-IRA, potentially through its outputs to brainstem respiratory regions.

癫痫猝死 (SUDEP) 是难治性癫痫患者死亡的主要原因。从最近的人体研究和动物模型中积累的证据表明，癫痫发作相关的呼吸骤停可能对引发心肺骤停和死亡很重要。先前的证据表明，呼吸暂停的发作可能与癫痫发作扩散到杏仁核同时发生，并且刺激杏仁核可以可靠地诱发癫痫患者的呼吸暂停，这可能表明杏仁核区域与癫痫发作相关的呼吸骤停以及随后的发作后通气不足和心肺死亡有关。本研究旨在使用 DBA/1 小鼠确定扩展的杏仁核结构，即终纹背侧床核 (dBNST)，是否参与癫痫发作引起的呼吸骤停 (S-IRA) 和死亡，一种具有听源性癫痫发作 (AGS) 和发作后呼吸骤停和死亡高发率的小鼠品系。S-IRA 的存在显着增加了 DBA/1 小鼠 dBNST 中的 c-Fos 表达。此外，通过病毒诱导的破伤风神经毒素 (TeNT) 破坏 dBNST 的突触输出显着提高了 DBA/1 小鼠 S-IRA 后的存活率，而不影响基线呼吸或高碳酸血症 (HCVR) 和缺氧通气反应 (HVR)。dBNST 的这种破坏导致臂旁外侧核 (PBN) 和导水管周围灰质 (PAG) 的下游脑干区域中兴奋性/抑制性 (E/I) 突触事件的平衡发生变化。这些发现表明 dBNST 是调节 S-IRA 所必需的潜在皮质下前脑位点，