Department of Neurologic Surgery, Mayo Clinic, 200 First Street SW, Rochester, MN 55902, USA.
J Neural Eng. 2011 Aug;8(4):046001. doi: 10.1088/1741-2560/8/4/046001. Epub 2011 May 27.
Deep brain stimulation (DBS) of the thalamus has been demonstrated to be effective for the treatment of epilepsy. To investigate the mechanism of action of thalamic DBS, we examined the effects of high frequency stimulation (HFS) on spindle oscillations in thalamic brain slices from ferrets. We recorded intracellular and extracellular electrophysiological activity in the nucleus reticularis thalami (nRt) and in thalamocortical relay (TC) neurons in the lateral geniculate nucleus, stimulated the slice using a concentric bipolar electrode, and recorded the level of glutamate within the slice. HFS (100 Hz) of TC neurons generated excitatory post-synaptic potentials, increased the number of action potentials in both TC and nRt neurons, reduced the input resistance, increased the extracellular glutamate concentration, and abolished spindle wave oscillations. HFS of the nRt also suppressed spindle oscillations. In both locations, HFS was associated with significant and persistent elevation in extracellular glutamate levels and suppressed spindle oscillations for many seconds after the cessation of stimulation. We simulated HFS within a computational model of the thalamic network, and HFS also disrupted spindle wave activity, but the suppression of spindle activity was short-lived. Simulated HFS disrupted spindle activity for prolonged periods of time only after glutamate release and glutamate-mediated activation of a hyperpolarization-activated current (I(h)) was incorporated into the model. Our results suggest that the mechanism of action of thalamic DBS as used in epilepsy may involve the prolonged release of glutamate, which in turn modulates specific ion channels such as I(h), decreases neuronal input resistance, and abolishes thalamic network oscillatory activity.
丘脑深部电刺激 (DBS) 已被证明对治疗癫痫有效。为了研究丘脑 DBS 的作用机制，我们研究了高频刺激 (HFS) 对雪貂丘脑脑片纺锤波振荡的影响。我们记录了丘脑网状核 (nRt) 和外侧膝状体丘脑皮质中继 (TC) 神经元的细胞内和细胞外电生理活动，使用同心双极电极刺激切片，并记录切片内谷氨酸的水平。TC 神经元的 HFS (100 Hz) 产生兴奋性突触后电位，增加 TC 和 nRt 神经元的动作电位数量，降低输入电阻，增加细胞外谷氨酸浓度，并消除纺锤波振荡。nRt 的 HFS 也抑制了纺锤波振荡。在这两个位置，HFS 与细胞外谷氨酸水平的显著和持续升高相关，并在刺激停止后持续数秒抑制纺锤波振荡。我们在丘脑网络的计算模型中模拟了 HFS，HFS 也破坏了纺锤波活动，但抑制纺锤活动是短暂的。只有在将谷氨酸释放和谷氨酸介导的超极化激活电流 (I(h)) 激活纳入模型后，模拟的 HFS 才会在较长时间内破坏纺锤活动。我们的结果表明，用于癫痫治疗的丘脑 DBS 的作用机制可能涉及谷氨酸的长时间释放，这反过来又调节特定的离子通道，如 I(h)，降低神经元输入电阻，并消除丘脑网络振荡活动。
