在光遗传学诱导癫痫发作的小鼠模型中，γ-氨基丁酸能中间神经元的动态、细胞类型特异性作用
Dynamic, Cell-Type-Specific Roles for GABAergic Interneurons in a Mouse Model of Optogenetically Inducible Seizures.
作者信息
Khoshkhoo Sattar, Vogt Daniel, Sohal Vikaas S
机构信息
Department of Psychiatry, University of California, San Francisco, San Francisco, CA 94143-0444, USA; Weil Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94143-0444, USA; Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, CA 94143-0444, USA; Sloan Swartz Center for Theoretical Neurobiology, University of California, San Francisco, San Francisco, CA 94143-0444, USA.
Department of Psychiatry, University of California, San Francisco, San Francisco, CA 94143-0444, USA; Weil Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94143-0444, USA; Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, CA 94143-0444, USA.
出版信息
Neuron. 2017 Jan 18;93(2):291-298. doi: 10.1016/j.neuron.2016.11.043. Epub 2016 Dec 29.
GABAergic interneurons play critical roles in seizures, but it remains unknown whether these vary across interneuron subtypes or evolve during a seizure. This uncertainty stems from the unpredictable timing of seizures in most models, which limits neuronal imaging or manipulations around the seizure onset. Here, we describe a mouse model for optogenetic seizure induction. Combining this with calcium imaging, we find that seizure onset rapidly recruits parvalbumin (PV), somatostatin (SOM), and vasoactive intestinal peptitde (VIP)-expressing interneurons, whereas excitatory neurons are recruited several seconds later. Optogenetically inhibiting VIP interneurons consistently increased seizure threshold and reduced seizure duration. Inhibiting PV+ and SOM+ interneurons had mixed effects on seizure initiation but consistently reduced seizure duration. Thus, while their roles may evolve during seizures, PV+ and SOM+ interneurons ultimately help maintain ongoing seizures. These results show how an optogenetically induced seizure model can be leveraged to pinpoint a new target for seizure control: VIP interneurons. VIDEO ABSTRACT.
γ-氨基丁酸能中间神经元在癫痫发作中起关键作用，但这些作用是否因中间神经元亚型而异或在癫痫发作过程中发生演变仍不清楚。这种不确定性源于大多数模型中癫痫发作时间的不可预测性，这限制了在癫痫发作开始时进行神经元成像或操作。在此，我们描述了一种用于光遗传学诱导癫痫发作的小鼠模型。将其与钙成像相结合，我们发现癫痫发作开始时迅速招募了表达小白蛋白（PV）、生长抑素（SOM）和血管活性肠肽（VIP）的中间神经元，而兴奋性神经元在数秒后才被招募。光遗传学抑制VIP中间神经元持续提高癫痫发作阈值并缩短癫痫发作持续时间。抑制PV+和SOM+中间神经元对癫痫发作起始有混合效应，但持续缩短癫痫发作持续时间。因此，虽然它们的作用可能在癫痫发作过程中发生演变，但PV+和SOM+中间神经元最终有助于维持正在进行的癫痫发作。这些结果表明如何利用光遗传学诱导的癫痫模型来确定癫痫控制的新靶点：VIP中间神经元。视频摘要。
Zotero 插件