Restoring failed inhibition in the substantia nigra pars reticulata suppresses absence seizures in rats

Objective For over four decades, the substantia nigra pars reticulata (SNr) has been recognized as a critical structure in the modulation of seizure activity. Pharmacological and optogenetic inhibition of the SNr produce robust seizure suppression in a range of seizure models. These findings have given rise to a longstanding, yet unresolved question: do seizures involve a failure of inhibition within the SNr? Methods We recorded single-unit activity in the SNr during spike-and-wave discharges (SWDs) in male and female WAG/Rij rats, a model of genetic absence epilepsy. We monitored extracellular GABA levels using intensity-based GABA sensing fluorescence reporter (iGABASnFR). To emphasize the multi-modal efficacy of SNr inhibition on seizure suppression, we optogenetically inhibited the SNr. Results 50% of recorded neurons exhibited a marked increase in firing at SWD onset, with activity returning to baseline at SWD termination. Extracellular GABA levels revealed a decrease in fluorescen..., , # Data from: Restoring failed inhibition in the substantia nigra pars reticulata suppresses absence seizures in rats Dataset DOI: [10.5061/dryad.66t1g1kds](https://doi.org/10.5061/dryad.66t1g1kds) ## Description of the data and file structure #### File: SNr.Optogenetics.zip **Description:** A zip archive with folders containing European Data Format (EDF) electroencephalography (EEG) files for each test session for each subject, organized by virus. Files show a full baseline, 100Hz Open Loop or 100Hz Closed Loop session for each animal with electrographic activity recorded from cortical EEG and stimulator feedback (when relevant)showing the timing of light delivery and closed loop macro seizure detection (when relevant). Data are organized into two separate folders based on virus used. * “GFP.Control” are recordings from animals injected with a control AAV virus expressing green fluorescent protein but no opsin. * “ArchT” are recordings from animals injected with AAV coding for arc...,### 研究目标 四十余年来，黑质网状部（substantia nigra pars reticulata, SNr）已被证实是调控痫性发作活动的关键脑区。针对黑质网状部的药理学与光遗传学抑制手段，在多种痫性发作模型中均能实现显著的痫性发作抑制。上述研究结论引出了一个长期存在却尚未解决的科学问题：痫性发作是否伴随着黑质网状部内的抑制功能失效？ ### 研究方法 本研究在遗传性失神癫痫模型WAG/Rij雌雄大鼠的棘慢波放电（spike-and-wave discharges, SWDs）期间，记录了黑质网状部内的单神经元活动。我们采用基于强度传感的γ-氨基丁酸荧光报告基因（intensity-based GABA sensing fluorescence reporter, iGABASnFR），对细胞外γ-氨基丁酸（GABA）水平进行监测。为了验证黑质网状部抑制手段在痫性发作抑制中的多模态有效性，我们采用光遗传学手段对黑质网状部进行抑制。 ### 研究结果 在记录到的神经元中，有50%在棘慢波放电发作时放电频率显著升高，并在棘慢波放电结束时恢复至基线水平。细胞外γ-氨基丁酸水平检测结果显示荧光信号下降…… 数据来源：《恢复黑质网状部的抑制功能失效可抑制大鼠失神癫痫》（Restoring failed inhibition in the substantia nigra pars reticulata suppresses absence seizures in rats） 数据集DOI：[10.5061/dryad.66t1g1kds](https://doi.org/10.5061/dryad.66t1g1kds) ## 数据与文件结构说明 #### 数据文件：SNr.Optogenetics.zip **文件说明：** 该压缩包内包含按病毒载体分组的文件夹，每个文件夹内存储了对应受试动物各测试时段的欧洲数据格式（European Data Format, EDF）脑电图（electroencephalography, EEG）文件。每份文件包含完整的基线期、100Hz开环或100Hz闭环测试时段的脑电数据，记录了皮层脑电图的脑电活动，以及刺激器反馈信息（若适用），其中标注了光刺激递送的时间点与闭环大发作检测结果（若适用）。 本数据集按照所用病毒载体分为两个独立文件夹： * "GFP.Control"文件夹：存储了注射了仅表达绿色荧光蛋白、不含视蛋白的对照腺相关病毒（adeno-associated virus, AAV）的受试动物的脑电记录数据。 * "ArchT"文件夹：存储了注射了编码……的腺相关病毒的受试动物的脑电记录数据。