Subthalamic high frequency stimulation resets subthalamic firing and reduces abnormal oscillations
Subthalamic high frequency stimulation resets subthalamic firing and reduces abnormal oscillations
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DOI：
10.1093/brain/awh616
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发表时间：
2005-10-01
期刊：
影响因子：
14.5
通讯作者：
Boraud, T
中科院分区：
文献类型：
--
作者：
Meissner, W;Leblois, A;Boraud, T
丘脑底核的高频刺激(HFS)是治疗晚期帕金森病的一种成熟的治疗方法。尽管这种疾病的根本原因仍然是一个谜，但不同基底节核团的放电频率和同步活动的变化与其症状有关。在这里，我们利用细胞外单位同步记录的方法，研究了STN-HFS对1-甲基-4-苯基-1，2，3，6-四氢吡啶(MPTP)损伤的非人灵长类动物STN网络放电频率以及相关和振荡活动的影响。STN-HFS降低(1)STN神经元的放电频率，(2)单个STN神经元水平的振荡活动，以及(3)对侧STN神经元之间的相关和振荡活动，而对侧刚性则得到改善。详细的分析表明，平均射速的降低是由于刺激脉冲将射击概率重置为几乎为零造成的。随后，STN神经元在平均持续时间2.9+/-0.1ms后恢复活动，其放电概率恢复到与刺激脉冲开始后7ms相似的基线值，放电概率的恢复用S型函数表示。因此，平均放电频率的总体下降是由于以130赫兹的频率重复这一动态过程(刺激间间隔类似于7.7ms)，使得神经元仅在非常短的时间内以其基线放电速率放电。虽然STN网络中神经元活动去同步化的机制尚不清楚，但电刺激对STN神经元放电概率的重置可能会增加单个神经元水平的振荡活动，以及STN神经元对之间的相互关联和振荡活动。然而，假设放电频率的重置是通过兴奋突触前GABA能轴突终末而产生一过性GABA能抑制的结果，不同的STN神经元的恢复周期可能会延迟同步振荡的出现，特别是如果它们不是在局部产生的。总之，我们的研究为STN-HFS降低STN网络中的振荡活动提供了新的证据。虽然振荡活动与帕金森病症状之间的确切关系仍未确定，但目前的结果表明，STN-HFS可能至少部分地通过减少STN网络的振荡活动从而减少整个皮质-基底节-皮质网络的振荡活动而发挥其有益的作用。
High frequency stimulation (HFS) of the subthalamic nucleus (STN) is a well-established therapeutic approach for the treatment of late-stage Parkinson's disease. Although the underlying cause of this illness remains a mystery, changes in firing rate and synchronized activity in different basal ganglia nuclei have been related to its symptoms. Here we investigated the impact of STN-HFS on firing rate as well as correlated and oscillatory activity in the STN network in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned non-human primates by using simultaneous extracellular single-unit recordings. STN-HFS reduced (i) the firing rate of STN neurons, (ii) the oscillatory activity at an individual STN neuron level as well as (iii) the correlated and oscillatory activity between pairs of STN neurons, while contralateral rigidity was improved. A detailed analysis showed that the decrease of mean firing rate resulted from the resetting of firing probability to virtually zero by the stimulus pulse. Subsequently, STN neurons resumed their activity after a mean duration of 2.9 +/- 0.1 ms and their firing probability returned to baseline values similar to 7 ms after the onset of the stimulus pulse, the recovery of the firing probability being represented by a sigmoid function. Thus, the overall decrease of the mean firing rate resulted from the repetition of this dynamical process with a frequency of 130 Hz (interstimulus interval similar to 7.7 ms), allowing the neuron to fire with its baseline firing rate only for a very short period. Although the mechanisms underlying the desynchronization of neuronal activity in the STN network remain unclear, the resetting of STN neuron firing probability by the electrical stimulus would rather be expected to increase oscillatory activity at an individual neuron level as well as correlated and oscillatory activity between pairs of STN neurons. However, assuming the resetting of firing rate to be the consequence of a transient GABAergic inhibition through excitation of presynaptic GABAergic axon terminals, different recovery periods of STN neurons might delay the appearance of synchronized oscillations, particularly if they are not generated locally. In conclusion, our study provides new evidence that STN-HFS decreases oscillatory activity in the STN network. Although the exact relation between oscillatory activity and Parkinson's disease symptoms remains to be determined, the present results suggest that STN-HFS might at least partially exert its beneficial effects through the reduction of oscillatory activity in the STN network and consequently in the entire cortex-basal ganglia-cortex network.