Selective optogenetic stimulation of efferent fibers in the vagus nerve of a large mammal.
Selective optogenetic stimulation of efferent fibers in the vagus nerve of a large mammal.
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DOI：
10.1016/j.brs.2020.11.010
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发表时间：
2021-01
影响因子：
7.7
通讯作者：
Gourine AV
中科院分区：
文献类型：
--
作者：
Booth LC;Yao ST;Korsak A;Farmer DGS;Hood SG;McCormick D;Boesley Q;Connelly AA;McDougall SJ;Korim WS;Guild SJ;Mastitskaya S;Le P;Teschemacher AG;Kasparov S;Ackland GL;Malpas SC;McAllen RM;Allen AM;May CN;Gourine AV
应用于单个器官、周围神经或特定大脑区域的电刺激已被用来治疗一系列疾病。在心血管疾病中，自主神经功能障碍会导致疾病进展，并且一直在寻求迷走神经电刺激作为恢复自主神经平衡的治疗方法。然而，这种方法在激活功能和器官特异性迷走纤维方面缺乏选择性，尽管许多临床前研究取得了有希望的结果，但迄今为止未能转化为心血管疾病的临床治疗。在这里，我们报告了光遗传学在大型动物模型（绵羊）中选择性刺激迷走神经传出活动的成功应用。病毒转导迷走神经运动神经元子集十二周后，兴奋性光敏离子通道 ChIEF 的轴突膜在支配胸腔器官的传出投射中实现强表达，并超出膈肌水平。施加到颈部迷走神经的蓝色激光或 LED 光（>10 mW mm−2；1 ms 脉冲）触发精确定时的强烈传出活动爆发，诱发动作电位以 ∼6 m s−1 的速度传播。这些发现表明，在具有大的多束迷走神经的物种中，可以在远离载体传递的部位使用光刺激特定的传出纤维亚群，这标志着光遗传学技术最终应用于自主神经调节的临床应用迈出了重要一步。描述了一种使用光选择性传出迷走神经刺激的方法。迷走神经节前神经元的目标是表达光敏感通道。在大型动物模型中，通过将光传递到颈部迷走神经来实现特定的传出 VNS。展示了使用光遗传学技术进行自主神经调节的可行性。
Electrical stimulation applied to individual organs, peripheral nerves, or specific brain regions has been used to treat a range of medical conditions. In cardiovascular disease, autonomic dysfunction contributes to the disease progression and electrical stimulation of the vagus nerve has been pursued as a treatment for the purpose of restoring the autonomic balance. However, this approach lacks selectivity in activating function- and organ-specific vagal fibers and, despite promising results of many preclinical studies, has so far failed to translate into a clinical treatment of cardiovascular disease. Here we report a successful application of optogenetics for selective stimulation of vagal efferent activity in a large animal model (sheep). Twelve weeks after viral transduction of a subset of vagal motoneurons, strong axonal membrane expression of the excitatory light-sensitive ion channel ChIEF was achieved in the efferent projections innervating thoracic organs and reaching beyond the level of the diaphragm. Blue laser or LED light (>10 mW mm−2; 1 ms pulses) applied to the cervical vagus triggered precisely timed, strong bursts of efferent activity with evoked action potentials propagating at speeds of ∼6 m s−1. These findings demonstrate that in species with a large, multi-fascicled vagus nerve, it is possible to stimulate a specific sub-population of efferent fibers using light at a site remote from the vector delivery, marking an important step towards eventual clinical use of optogenetic technology for autonomic neuromodulation. Described is a method of selective efferent vagus nerve stimulation using light. Vagal preganglionic neurons are targeted to express light-sensitive channels. Specific efferent VNS by light delivery to the cervical vagus is achieved in a large animal model. Demonstrates feasibility of using optogenetic technology for autonomic neuromodulation.
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影响因子：
5.1
作者：
Benzekhroufa, K.;Liu, B-H;Kasparov, S.
通讯作者：
Kasparov, S.
影响因子：
3.4
作者：
Lin, John Y.;Lin, Michael Z.;Tsien, Roger Y.
通讯作者：
Tsien, Roger Y.
影响因子：
--
作者：
HOFFMAN, HH;SCHNITZLEIN, HN
通讯作者：
SCHNITZLEIN, HN
DOI：
10.1126/science.aan5544
发表时间：
2017-09-15
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Deisseroth K;Hegemann P
通讯作者：
Hegemann P
影响因子：
16.6
作者：
Machhada A;Trapp S;Marina N;Stephens RCM;Whittle J;Lythgoe MF;Kasparov S;Ackland GL;Gourine AV
通讯作者：
Gourine AV