Meissner Wassilios, Leblois Arthur, Hansel David, Bioulac Bernard, Gross Christian E, Benazzouz Abdelhamid, Boraud Thomas
Basal Gang, Laboratoire de Neurophysiologie, CNRS UMR 5543, Université Victor Ségalen, Bordeaux, France.
Brain. 2005 Oct;128(Pt 10):2372-82. doi: 10.1093/brain/awh616. Epub 2005 Aug 25.
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 approximately 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 approximately 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.
丘脑底核高频刺激(STN-HFS)是治疗晚期帕金森病的一种成熟治疗方法。尽管这种疾病的根本原因仍是个谜,但不同基底神经节核团的放电频率变化和同步活动与其症状有关。在此,我们通过同时进行细胞外单单元记录,研究了STN-HFS对1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)损伤的非人类灵长类动物丘脑底核网络中放电频率以及相关和振荡活动的影响。STN-HFS降低了(i)丘脑底核神经元的放电频率,(ii)单个丘脑底核神经元水平的振荡活动以及(iii)丘脑底核神经元对之间的相关和振荡活动,同时对侧僵硬症状得到改善。详细分析表明,平均放电频率的降低是由于刺激脉冲将放电概率重置为几乎零所致。随后,丘脑底核神经元在平均持续时间2.9±0.1毫秒后恢复活动,其放电概率在刺激脉冲开始后约7毫秒恢复到基线值,放电概率的恢复由一个S形函数表示。因此,平均放电频率的总体降低是由于以130赫兹的频率重复这个动态过程(刺激间隔约7.7毫秒),使得神经元仅在非常短的时间内以其基线放电频率放电。尽管丘脑底核网络中神经元活动去同步化的潜在机制仍不清楚,但电刺激对丘脑底核神经元放电概率的重置预计会增加单个神经元水平的振荡活动以及丘脑底核神经元对之间的相关和振荡活动。然而,假设放电频率的重置是通过兴奋突触前GABA能轴突终末导致的短暂GABA能抑制的结果,丘脑底核神经元不同的恢复时间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话。总之,我们的研究提供了新的证据,表明STN-HFS降低了丘脑底核网络中的振荡活动。尽管振荡活动与帕金森病症状的确切关系仍有待确定,但目前的结果表明,STN-HFS可能至少部分地通过降低丘脑底核网络以及整个皮质-基底神经节-皮质网络中的振荡活动来发挥其有益作用。
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