Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA.
Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA; Department of Bioengineering, Stanford University, Stanford, CA 94305, USA; Department of Neurosurgery, Stanford University, Stanford, CA 94305, USA; Department of Electrical Engineering, Stanford University, Stanford, CA 94305, USA.
Cell Rep. 2020 Feb 25;30(8):2540-2554.e4. doi: 10.1016/j.celrep.2020.01.095.
To understand the conditions necessary to initiate and terminate seizures, we investigate optogenetically induced hippocampal seizures with LFP, fMRI, and optogenetic inhibition. During afterdischarge induction using optogenetics, LFP recordings show that stimulations with earlier ictal onset times are more likely to result in afterdischarges and are more difficult to curtail with optogenetic inhibition. These results are generalizable across two initiation sites, the dorsal and ventral hippocampus. fMRI shows that afterdischarges initiated from the dorsal or ventral hippocampus exhibit distinct networks. Short-duration seizures initiated in the dorsal and ventral hippocampus are unilateral and bilateral, respectively, while longer-duration afterdischarges recruit broader, bilateral networks. When optogenetic inhibition is ineffective at stopping seizures, the network activity spreads more extensively but largely overlaps with the network activity associated with seizures that could be curtailed. These results provide insights into how seizures can be inhibited, which has implications for targeted seizure interventions.
为了理解引发和终止癫痫发作所需的条件,我们使用 LFPs、fMRI 和光遗传学抑制来研究光遗传学诱导的海马体癫痫发作。在使用光遗传学进行发作后放电诱导时,LFP 记录显示,发作起始时间较早的刺激更有可能导致发作后放电,并且用光遗传学抑制来抑制这些放电更加困难。这些结果在两个起始部位(背侧和腹侧海马体)之间具有普遍性。fMRI 显示,来自背侧或腹侧海马体的发作后放电表现出不同的网络。在背侧和腹侧海马体中引发的短持续时间发作分别为单侧和双侧,而较长持续时间的发作后放电则招募更广泛的双侧网络。当光遗传学抑制不能有效阻止癫痫发作时,网络活动传播得更广泛,但主要与可以抑制的癫痫发作相关的网络活动重叠。这些结果提供了对如何抑制癫痫发作的深入了解,这对有针对性的癫痫发作干预具有重要意义。