Cerebellar output controls generalized spike-and-wave discharge occurrence.
Cerebellar output controls generalized spike-and-wave discharge occurrence.
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DOI：
10.1002/ana.24399
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发表时间：
2015-06
影响因子：
11.2
通讯作者：
Hoebeek, Freek E.
中科院分区：
文献类型：
--
作者：
Kros, Lieke;Rooda, Oscar H. J. Eelkman;Spanke, Jochen K.;Alva, Parimala;van Dongen, Marijn N.;Karapatis, Athanasios;Tolner, Else A.;Strydis, Christos;Davey, Neil;Winkelman, Beerend H. J.;Negrello, Mario;Serdijn, Wouter A.;Steuber, Volker;van den Maagdenberg, Arn M. J. M.;De Zeeuw, Chris I.;Hoebeek, Freek E.
破坏丘脑皮层活动模式已被证明是一种有前途的方法，以停止全身性棘波放电（GSWD）的特点失神发作。在这里，我们调查到什么程度的调制小脑核（CN），这是在解剖学上的有利位置，通过他们的神经支配的各种丘脑核，破坏皮层振荡的神经元放电，是有效的控制失神发作。使用了两种不相关的全身失神发作小鼠模型：自然突变体蹒跚，其特征在于Cacna 1a中的错义突变，和近交系C3 H/HeOuJ。在清醒动物中同时记录单个CN神经元活动和皮层脑电图的同时，我们研究了CN神经元活动的增加或减少在多大程度上可以调节GSWD的发生，以及短暂的按需CN刺激可以破坏癫痫发作。我们发现CN神经元的一个子集在GSWD期间显示锁相振荡放电，并且操纵这种活动调节GSWD的发生。通过局部应用γ-氨基丁酸A型（GABA-A）激动剂蝇蕈醇抑制CN神经元动作电位放电使GSWD发生率增加了37倍，而使用GABA-A拮抗剂gabazine增加CN神经元放电的频率和规律性使其发生率大幅下降。对CN神经元活动的单一短暂（30-300毫秒）光遗传学刺激会突然停止GSWD，即使是单方面施加也是如此。使用闭环系统，GSWD在500毫秒内被检测并停止。CN神经元是失神发作期间丘脑皮质网络活动病理振荡的有效调节剂，应评估其控制其他类型全身性癫痫的潜在治疗益处。神经学年鉴2015;77：1027-1049
Disrupting thalamocortical activity patterns has proven to be a promising approach to stop generalized spike‐and‐wave discharges (GSWDs) characteristic of absence seizures. Here, we investigated to what extent modulation of neuronal firing in cerebellar nuclei (CN), which are anatomically in an advantageous position to disrupt cortical oscillations through their innervation of a wide variety of thalamic nuclei, is effective in controlling absence seizures. Two unrelated mouse models of generalized absence seizures were used: the natural mutant tottering, which is characterized by a missense mutation in Cacna1a, and inbred C3H/HeOuJ. While simultaneously recording single CN neuron activity and electrocorticogram in awake animals, we investigated to what extent pharmacologically increased or decreased CN neuron activity could modulate GSWD occurrence as well as short‐lasting, on‐demand CN stimulation could disrupt epileptic seizures. We found that a subset of CN neurons show phase‐locked oscillatory firing during GSWDs and that manipulating this activity modulates GSWD occurrence. Inhibiting CN neuron action potential firing by local application of the γ‐aminobutyric acid type A (GABA‐A) agonist muscimol increased GSWD occurrence up to 37‐fold, whereas increasing the frequency and regularity of CN neuron firing with the use of GABA‐A antagonist gabazine decimated its occurrence. A single short‐lasting (30–300 milliseconds) optogenetic stimulation of CN neuron activity abruptly stopped GSWDs, even when applied unilaterally. Using a closed‐loop system, GSWDs were detected and stopped within 500 milliseconds. CN neurons are potent modulators of pathological oscillations in thalamocortical network activity during absence seizures, and their potential therapeutic benefit for controlling other types of generalized epilepsies should be evaluated. Ann Neurol 2015;77:1027–1049
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影响因子：
82.9
作者：
Cope, David W.;Di Giovanni, Giuseppe;Fyson, Sarah J.;Orban, Gergely;Errington, Adam C.;Lorincz, Magor L.;Gould, Timothy M.;Carter, David A.;Crunelli, Vincenzo
通讯作者：
Crunelli, Vincenzo
影响因子：
1.9
作者：
Chkhenkeli, SA;Sramka, M;Chkhenkeli, IS
通讯作者：
Chkhenkeli, IS
影响因子：
17.1
作者：
Chow, Brian Y.;Boyden, Edward S.
通讯作者：
Boyden, Edward S.
影响因子：
5.6
作者：
Berg, Anne T.;Berkovic, Samuel F.;Scheffer, Ingrid E.
通讯作者：
Scheffer, Ingrid E.
DOI：
10.1523/jneurosci.2087-09.2009
发表时间：
2009-08-12
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Bagnall MW;Zingg B;Sakatos A;Moghadam SH;Zeilhofer HU;du Lac S
通讯作者：
du Lac S