Optogenetic stimulation of cholinergic brainstem neurons during focal limbic seizures: Effects on cortical physiology.
Optogenetic stimulation of cholinergic brainstem neurons during focal limbic seizures: Effects on cortical physiology.
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DOI：
10.1111/epi.13220
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发表时间：
2015-12
期刊：
影响因子：
5.6
通讯作者：
Blumenfeld H
中科院分区：
文献类型：
--
作者：
Furman M;Zhan Q;McCafferty C;Lerner BA;Motelow JE;Meng J;Ma C;Buchanan GF;Witten IB;Deisseroth K;Cardin JA;Blumenfeld H
局灶性颞叶癫痫发作通常会导致皮质功能受损和意识丧失。最近的研究表明，在局灶性癫痫发作期间，皮质功能低下的机制可能取决于皮质下胆碱能唤醒的减少，这导致皮质慢波活动的睡眠样状态。为了验证这一假设，我们试图在局灶性边缘癫痫发作期间直接激活皮质下胆碱能神经元，以确定对皮质功能的影响。在这里，我们使用了光遗传学的方法，选择性地刺激胆碱能脑干神经元在脚桥被盖核局灶性边缘癫痫发作在轻度麻醉大鼠模型中诱导。我们发现，增加皮质γ活性和减少δ活性响应胆碱能刺激。这些发现支持了癫痫发作时皮质下胆碱能唤醒减少导致皮质功能障碍的机制作用。通过进一步的工作，皮层下唤醒网络的电或光遗传学刺激可能最终导致旨在预防癫痫发作期间皮层功能障碍的新治疗方法。
Focal temporal lobe seizures often cause impaired cortical function and loss of consciousness. Recent work suggests that the mechanism for depressed cortical function during focal seizures may depend on decreased subcortical cholinergic arousal, which leads to a sleep-like state of cortical slow-wave activity. To test this hypothesis, we sought to directly activate subcortical cholinergic neurons during focal limbic seizures to determine the effects on cortical function. Here we used an optogenetic approach to selectively stimulate cholinergic brainstem neurons in the pedunculopontine tegmental nucleus during focal limbic seizures induced in a lightly anesthetized rat model. We found an increase in cortical gamma activity and a decrease in delta activity in response to cholinergic stimulation. These findings support the mechanistic role of reduced subcortical cholinergic arousal in causing cortical dysfunction during seizures. Through further work, electrical or optogenetic stimulation of subcortical arousal networks may ultimately lead to new treatments aimed at preventing cortical dysfunction during seizures.