Magariños-Ascone C, Pazo J H, Macadar O, Buño W
Neurologi;a Experimental, Unidad Asociada al Instituto Cajal, CSIC, Depto. de Investigación, Hospital Ramón y Cajal, Ctra. Colmenar, 28034, Madrid, Spain.
Neuroscience. 2002;115(4):1109-17. doi: 10.1016/s0306-4522(02)00538-9.
The subthalamic nucleus participates in the control of movement and is considered a surgical target in the treatment of parkinsonian symptoms. Using the rat brain in vitro slice technique we show that sustained high-frequency (>100 Hz) electrical stimulation (i.e., 'tetanic stimulation') of the nucleus, as used in humans to treat Parkinson's disease, silenced subthalamic neurons. Two main cell types were identified. 'Tonic cells' (68%) showed delayed inward rectification, fired continuously, switched to bursting and stopped firing when strongly depolarized with injected current. Tetanic stimulation of the nucleus induced a steady depolarization (approximately 18 mV) that triggered action potentials at a high rate followed by bursts and finally (approximately 25 s) totally silenced tonic cells. The control tonic activity was recovered rapidly (<10 s) after ending stimulation. 'Phasic cells' (25%) discharged a single initial brief burst of action potentials both when depolarized by prolonged current injection and tetanic stimulation and did not show inward rectification. An infrequent cell type called 'phasic-tonic' (7%) showed a mixed discharge. We suggest that the silencing effect of tetanic stimulation is not a frequency-dependent presynaptic depression and could result from the gradual inactivation of Na+-mediated action potentials. These findings suggest that the remission of parkinsonian symptoms by treatment with high-frequency electrical stimulation of the subthalamic nucleus in humans may primarily reside on its capacity to suppress the action potential activity of subthalamic neurons.
丘脑底核参与运动控制，被认为是治疗帕金森症状的手术靶点。我们采用大鼠脑片体外技术表明，人类治疗帕金森病时所用的对该核的持续高频（>100Hz）电刺激（即“强直刺激”）会使丘脑底核神经元沉默。识别出了两种主要细胞类型。“紧张性细胞”（68%）表现出延迟内向整流，持续放电，在被注入电流强烈去极化时转为爆发式放电并停止放电。对丘脑底核的强直刺激诱导出稳定的去极化（约18mV），引发高速动作电位，随后是爆发式放电，最终（约25秒）使紧张性细胞完全沉默。刺激结束后，紧张性细胞的控制活动迅速恢复（<10秒）。“相位性细胞”（25%）在被长时间电流注入和强直刺激去极化时均会发出单次初始短暂动作电位爆发，且不表现内向整流。一种罕见的细胞类型“相位 - 紧张性细胞”（7%）表现出混合放电。我们认为强直刺激的沉默效应不是频率依赖性突触前抑制，可能是由Na⁺介导的动作电位逐渐失活导致的。这些发现表明，人类通过高频电刺激丘脑底核治疗帕金森症状的缓解可能主要在于其抑制丘脑底核神经元动作电位活动的能力。
