Optogenetic activation of the superior colliculus attenuates spontaneous seizures in the pilocarpine model of temporal lobe epilepsy.
Optogenetic activation of the superior colliculus attenuates spontaneous seizures in the pilocarpine model of temporal lobe epilepsy.
复制标题
上丘的光遗传学激活可减弱颞叶癫痫毛果芸香碱模型中的自发性癫痫发作。
DOI：
10.1111/epi.17469
复制
发表时间：
2023
期刊：
影响因子：
5.6
通讯作者：
Forcelli,PatrickA
中科院分区：
文献类型：
--
作者：
Hyder,SafwanK;Ghosh,Anjik;Forcelli,PatrickA
目的大量研究表明，在多种癫痫实验模型中，激活上丘深层和中间层可抑制癫痫发作。然而，以前的研究还没有检验对自发性边缘癫痫的疗效。本研究旨在通过慢性光遗传激活匹罗卡品诱导的颞叶癫痫模型的上丘来解决这一缺陷。方法SD大鼠采用匹罗卡品诱导的癫痫持续状态，并维持到自发发作。将编码通道视紫红质-2的病毒注射到上丘的深层和中间层，并在同一位置植入头戴式发光二极管。用5赫兹或100赫兹的光刺激大鼠。结果5和100 Hz光遗传刺激上丘深、中层均可减少动物每日癫痫发作次数和总癫痫发作负担。刺激既不影响发作持续时间，也不影响行为发作严重程度。在匹罗卡品所致的颞叶癫痫模型中，激活上丘的深层和中间层可减少癫痫发作次数和每日总发作负担。这些新的数据显示了对抗慢性实验性癫痫发作的效果，补充了长期以来记录上丘激活在一系列急性癫痫模型中的抗癫痫疗效的研究。
ObjectiveDecades of studies have indicated that activation of the deep and intermediate layers of the superior colliculus can suppress seizures in a wide range of experimental models of epilepsy. However, prior studies have not examined efficacy against spontaneous limbic seizures. The present study aimed to address this gap through chronic optogenetic activation of the superior colliculus in the pilocarpine model of temporal lobe epilepsy.MethodsSprague Dawley rats underwent pilocarpine‐induced status epilepticus and were maintained until the onset of spontaneous seizures. Virus coding for channelrhodopsin‐2 was injected into the deep and intermediate layers of the superior colliculus, and animals were implanted with head‐mounted light‐emitting diodes at the same site. Rats were stimulated with either 5‐ or 100‐Hz light delivery. Seizure number, seizure duration, 24‐h seizure burden, and behavioral seizure severity were monitored.ResultsBoth 5‐ and 100‐Hz optogenetic stimulation of the deep and intermediate layers of the superior colliculus reduced daily seizure number and total seizure burden in all animals in the active vector group. Stimulation did not affect either seizure duration or behavioral seizure severity. Stimulation was without effect in opsin‐negative control animals.SignificanceActivation of the deep and intermediate layers of the superior colliculus reduces both the number of seizures and total daily seizure burden in the pilocarpine model of temporal lobe epilepsy. These novel data demonstrating an effect against chronic experimental seizures complement a long history of studies documenting the antiseizure efficacy of superior colliculus activation in a range of acute seizure models.