Seizure reduction through interneuron-mediated entrainment using low frequency optical stimulation.
Seizure reduction through interneuron-mediated entrainment using low frequency optical stimulation.
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DOI：
10.1016/j.expneurol.2015.04.001
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发表时间：
2015-07
影响因子：
5.3
通讯作者：
Durand DM
中科院分区：
文献类型：
--
作者：
Ladas TP;Chiang CC;Gonzalez-Reyes LE;Nowak T;Durand DM
低频电刺激（LFS）可以降低动物和癫痫患者的神经兴奋性并抑制癫痫发作。然而，治疗结果可能受益于参与癫痫发作抑制的细胞类型的确定。我们利用光遗传学技术研究了中间神经元在致痫海马LFS（1Hz）中的作用。光学低频刺激（oLFS）首先用于激活Thy 1-ChR 2转基因小鼠中的阳离子通道通道视紫红质-2（ChR 2），所述转基因小鼠在兴奋性和抑制性神经元中表达ChR 2。我们发现oLFS可以有效地减少癫痫样活动在海马通过激活GAD表达的海马中间神经元。使用VGAT-ChR 2转基因小鼠证实了这一点，允许仅GABA中间神经元的选择性光学激活。通过oLFS激活海马中间神经元被发现引起类似于电刺激的神经活动的夹带，但通过GABAA介导的机制。这些结果证实了LFS范式的稳健性，并表明GABA中间神经元在塑造发作间期活动以降低海马中的神经兴奋性方面发挥了意想不到的作用。
Low frequency electrical stimulation (LFS) can reduce neural excitability and suppress seizures in animals and patients with epilepsy. However the therapeutic outcome could benefit from the determination of the cell types involved in seizure suppression. We used optogenetic techniques to investigate the role of interneurons in LFS (1Hz) in the epileptogenic hippocampus. Optical low frequency stimulation (oLFS) was first used to activate the cation channel channelrhodopsin-2 (ChR2) in the Thy1-ChR2 transgenic mouse that expresses ChR2 in both excitatory and inhibitory neurons. We found that oLFS could effectively reduce epileptiform activity in the hippocampus through the activation of GAD-expressing hippocampal interneurons. This was confirmed using the VGAT-ChR2 transgenic mouse, allowing for selective optical activation of only GABA interneurons. Activating hippocampal interneurons through oLFS was found to cause entrainment of neural activity similar to electrical stimulation, but through a GABAA-mediated mechanism. These results confirm the robustness of the LFS paradigm and indicate that GABA interneurons play an unexpected role of shaping inter-ictal activity to decrease neural excitability in the hippocampus.
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