Entorhinal Principal Neurons Mediate Brain-stimulation Treatments for Epilepsy.
Entorhinal Principal Neurons Mediate Brain-stimulation Treatments for Epilepsy.
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内嗅主神经元介导脑刺激治疗癫痫
DOI：
10.1016/j.ebiom.2016.11.027
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发表时间：
2016-12
期刊：
影响因子：
11.1
通讯作者：
Chen, Zhong
中科院分区：
文献类型：
--
作者：
Xu, Zhenghao;Wang, Yi;Chen, Bin;Xu, Cenglin;Wu, Xiaohua;Wang, Ying;Zhang, Shihong;Hu, Weiwei;Wang, Shuang;Guo, Yi;Zhang, Xiangnan;Luo, Jianhong;Duan, Shumin;Chen, Zhong
脑刺激是癫痫的一种替代治疗方法。然而，其机制背后的神经回路仍然不清楚。我们发现，光遗传学激活（1 Hz）内嗅钙/钙调素依赖性蛋白激酶II α（CaMK II α）阳性神经元，而不是GABA能神经元，延迟海马癫痫发生和降低海马癫痫发作的严重程度，类似于内嗅低频电刺激（LFES）。内嗅CaMK Ⅱ α阳性神经元的光发生抑制可阻断LFES的抗癫痫作用。channelrhodopsin-2-eYFP标记的内嗅CaMKIIα阳性神经元主要靶向海马，这些纤维的激活降低了海马癫痫发作的严重程度。结合细胞外记录和药理学方法，我们发现激活内嗅CaMKIIα阳性神经元可诱导GABA介导的海马神经元抑制。局灶性海马GABA能神经元的光遗传激活模拟了这种神经元调节作用并降低了海马癫痫发作的严重程度，但抗癫痫作用弱于内嗅LFES，这可能是由于局灶性光刺激的空间神经元调节作用有限。我们的研究结果表明LFES治疗癫痫的神经元回路，这是由内嗅主神经元介导的。激活（1 Hz）内嗅CaMKIIα阳性神经元可全面激活海马GABA能神经元，具有抗癫痫作用。抑制内嗅CaMKIIα阳性神经元促进海马癫痫发作并阻断LFES的抗癫痫作用。局灶性激活（1 Hz）海马GABA能神经元具有抗癫痫作用，其作用弱于LFES。虽然内嗅-海马回路在颞叶癫痫中的重要性已经被认识了几十年，但内嗅神经元在海马癫痫发作中的作用仍然不清楚。通过光遗传学和细胞外记录技术，Xu等发现了一种内嗅主神经元介导的抗癫痫“海马-GABA能”神经回路，用于脑刺激治疗TLE。也就是说，电非选择性或光选择性激活（1 Hz）内嗅CaMKIIα阳性神经元（内嗅主神经元的一种亚型），全面兴奋海马GABA能神经元并具有抗癫痫作用，而光学抑制这些神经元促进海马癫痫发作并阻断内嗅电刺激治疗的抗癫痫作用。
Brain stimulation is an alternative treatment for epilepsy. However, the neuronal circuits underlying its mechanisms remain obscure. We found that optogenetic activation (1 Hz) of entorhinal calcium/calmodulin-dependent protein kinase II α (CaMKIIα)-positive neurons, but not GABAergic neurons, retarded hippocampal epileptogenesis and reduced hippocampal seizure severity, similar to that of entorhinal low-frequency electrical stimulation (LFES). Optogenetic inhibition of entorhinal CaMKIIα-positive neurons blocked the antiepileptic effect of LFES. The channelrhodopsin-2-eYFP labeled entorhinal CaMKIIα-positive neurons primarily targeted the hippocampus, and the activation of these fibers reduced hippocampal seizure severity. By combining extracellular recording and pharmacological methods, we found that activating entorhinal CaMKIIα-positive neurons induced the GABA-mediated inhibition of hippocampal neurons. Optogenetic activation of focal hippocampal GABAergic neurons mimicked this neuronal modulatory effect and reduced hippocampal seizure severity, but the anti-epileptic effect is weaker than that of entorhinal LFES, which may be due to the limited spatial neuronal modulatory effect of focal photo-stimulation. Our results demonstrate a glutamatergic-GABAergic neuronal circuit for LFES treatment of epilepsy, which is mediated by entorhinal principal neurons. Activating (1 Hz) entorhinal CaMKIIα-positive neurons globally excite hippocampal GABAergic neurons and are antiepileptic. Inhibiting entorhinal CaMKIIα-positive neurons promote hippocampal seizures and blocks antiepileptic effects of LFES. Focally activating (1 Hz) hippocampal GABAergic neuron is antiepileptic, which is weaker than LFES. Although the importance of the entorhinal-hippocampal circuit in TLE has been acknowledged for several decades, the role of entorhinal neurons in the hippocampal seizure remains obscure. By optogenetics and extracellular recording, Xu et al. discovered an entorhinal principal neurons mediated antiepileptic “glutamatergic-GABAergic” neuronal circuit for brain stimulation treatment of TLE. That is, electrical non-selectively or optical selectively activating (1 Hz) entorhinal CaMKIIα-positive neurons, a subtype of entorhinal principal neurons, globally excited hippocampal GABAergic neurons and had antiepileptic effects while optically inhibiting these neurons promoted hippocampal seizures and blocked the antiepileptic effect of entorhinal electrical stimulation treatment.
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影响因子：
5.3
作者：
GIACCHINO, JL;SOMJEN, GG;MCNAMARA, JO
通讯作者：
MCNAMARA, JO
影响因子：
16.6
作者：
通讯作者：
--
DOI：
10.1073/pnas.0608215103
发表时间：
2006-12-12
影响因子：
11.1
作者：
Klaassen, Alwin;Glykys, Joseph;Boulter, Jim
通讯作者：
Boulter, Jim
DOI：
10.1523/jneurosci.0092-12.2013
发表时间：
2013-01-16
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Kumar S;Black SJ;Hultman R;Szabo ST;DeMaio KD;Du J;Katz BM;Feng G;Covington HE 3rd;Dzirasa K
通讯作者：
Dzirasa K
影响因子：
25
作者：
Krook-Magnuson, Esther;Soltesz, Ivan
通讯作者：
Soltesz, Ivan