Response of human thalamic neurons to high-frequency stimulation.
Response of human thalamic neurons to high-frequency stimulation.
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DOI：
10.1371/journal.pone.0096026
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Grill WM
中科院分区：
文献类型：
--
作者：
Birdno MJ;Tang W;Dostrovsky JO;Hutchison WD;Grill WM
丘脑深部脑刺激（DBS）是治疗震颤的有效方法，但其作用机制尚不清楚。先前的研究表明，人类丘脑神经元在高频细胞外刺激停止后，会出现短暂的反弹爆发活动，随后会出现长时间的抑制，而本研究试图确定这种反应的机制。在6例帕金森病患者的DBS导联植入手术中，记录了13个丘脑神经元在短时细胞外刺激下的低阈值峰（LTS）爆发。停止刺激后的反应包括短暂的爆发活动，随后是长时间的沉默，然后再回到LTS爆发。一群丘脑皮质中继神经元和突触前轴突终止在神经元上的计算模型被用来确定观察到的反应的细胞机制。该模型包括神经调节剂的作用，通过抑制非百日咳毒素敏感的K+电流（IKL），激活百日咳毒素敏感的K+电流（IKG），以及超极化激活的阳离子电流（Ih）的激活曲线的移动。该模型很好地复制了测量到的反应，并且长时间的抑制与IKG的变化密切相关，而IKL或Ih的调节对刺激后抑制的影响最小，这表明响应高频刺激释放的神经调节剂介导了刺激后丘脑神经元的爆发和随后的长时间沉默。该模型还表明，尽管对胞体有抑制作用，但模型神经元的轴突对阈上刺激有强烈的反应。结果表明，在DBS过程中，丘脑皮层神经元轴突被激活，而细胞体被抑制，从而阻断病理信号通过网络的传递，代之以高频的有规律的放电。
Thalamic deep brain stimulation (DBS) is an effective treatment for tremor, but the mechanisms of action remain unclear. Previous studies of human thalamic neurons to noted transient rebound bursting activity followed by prolonged inhibition after cessation of high frequency extracellular stimulation, and the present study sought to identify the mechanisms underlying this response. Recordings from 13 thalamic neurons exhibiting low threshold spike (LTS) bursting to brief periods of extracellular stimulation were made during surgeries to implant DBS leads in 6 subjects with Parkinson's disease. The response immediately after cessation of stimulation included a short epoch of burst activity, followed by a prolonged period of silence before a return to LTS bursting. A computational model of a population of thalamocortical relay neurons and presynaptic axons terminating on the neurons was used to identify cellular mechanisms of the observed responses. The model included the actions of neuromodulators through inhibition of a non-pertussis toxin sensitive K+ current (IKL), activation of a pertussis toxin sensitive K+ current (IKG), and a shift in the activation curve of the hyperpolarization-activated cation current (Ih). The model replicated well the measured responses, and the prolonged inhibition was associated most strongly with changes in IKG while modulation of IKL or Ih had minimal effects on post-stimulus inhibition suggesting that neuromodulators released in response to high frequency stimulation are responsible for mediating the post-stimulation bursting and subsequent long duration silence of thalamic neurons. The modeling also indicated that the axons of the model neurons responded robustly to suprathreshold stimulation despite the inhibitory effects on the soma. The findings suggest that during DBS the axons of thalamocortical neurons are activated while the cell bodies are inhibited thus blocking the transmission of pathological signals through the network and replacing them with high frequency regular firing.
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