Filali Mohammed, Hutchison William D, Palter Vanessa N, Lozano Andres M, Dostrovsky Jonathan O
Department of Physiology, Rm. 3305 Medical Sciences Building, University of Toronto, University Health Network, 1 King's College Circle, M5S 1A8, Toronto, Ontario, Canada.
Exp Brain Res. 2004 Jun;156(3):274-81. doi: 10.1007/s00221-003-1784-y. Epub 2004 Jan 24.
The subthalamic nucleus (STN) is an important component of the basal ganglia (BG) and plays a major role in the pathogenesis of Parkinson's disease (PD). Hyperactivity of STN as a consequence of the loss of dopaminergic inputs to the BG is believed to be a major factor in producing the motor symptoms of PD. High-frequency (HF) deep brain stimulation (DBS) of the STN has recently become an important treatment in PD patients where medications no longer provide satisfactory therapy. However, the mechanisms underlying DBS therapy are unknown, and there is seemingly conflicting data suggesting inhibition or excitation of STN neurons. This study directly examined the effects of stimulation in STN on the activity of STN neurons in PD patients during functional stereotactic mapping prior to insertion of DBS electrodes. Electrical stimulation in STN was investigated in twelve PD patients by recording the neural activity of a cell in STN with one electrode while applying current pulses through a second electrode located about 600 microm away. Stimulation at high frequencies (100-300 Hz) was found to produce inhibition following the stimulus train in 42% of the 60 cells tested. Inhibition during the train was seen in 13 of 15 neurons where it was possible to detect such activity. Furthermore, in 44% of the cases where HF stimulation produced inhibition there was an early inhibition followed by rebound excitation and a further inhibitory period, suggesting that the inhibitions observed are due to hyperpolarization. In eight of the 25 neurons inhibited by HF stimulation, the effects of single stimuli were determined and revealed that in seven of these there was an inhibitory period of 15-20 ms following each stimulus. Thus, the present findings suggest that local HF stimulation inhibits many STN neurons. However, these studies could not determine whether the stimulus also directly excited the cell and/or its axon, but other recent findings suggest that this is likely the case. Therefore, the overall effects of DBS stimulation in STN are likely to be inhibition of intrinsic and synaptically mediated activity, and its replacement by regular high-frequency firing.
丘脑底核（STN）是基底神经节（BG）的重要组成部分，在帕金森病（PD）的发病机制中起主要作用。由于多巴胺能输入到BG的丧失导致STN活动亢进，被认为是产生PD运动症状的主要因素。STN的高频（HF）深部脑刺激（DBS）最近已成为PD患者的重要治疗方法，在这些患者中药物治疗不再提供令人满意的疗效。然而，DBS治疗的潜在机制尚不清楚，并且存在似乎相互矛盾的数据表明STN神经元受到抑制或兴奋。本研究在植入DBS电极之前，在功能立体定向映射期间直接检查了STN刺激对PD患者STN神经元活动的影响。通过用一个电极记录STN中一个细胞的神经活动，同时通过位于约600微米远处的第二个电极施加电流脉冲，对12名PD患者的STN进行电刺激研究。在测试的60个细胞中，42%的细胞在高频（100 - 300 Hz）刺激后的刺激序列后出现抑制。在15个神经元中的13个中观察到刺激期间的抑制，在这些神经元中可以检测到这种活动。此外，在HF刺激产生抑制的44%的病例中，存在早期抑制，随后是反弹兴奋和进一步的抑制期，这表明观察到的抑制是由于超极化。在25个受HF刺激抑制的神经元中的8个中，确定了单个刺激的效果，结果显示其中7个在每个刺激后有15 - 20毫秒的抑制期。因此，目前的研究结果表明局部HF刺激抑制许多STN神经元。然而，这些研究无法确定刺激是否也直接兴奋细胞和/或其轴突，但最近的其他研究结果表明可能是这种情况。因此，DBS刺激STN的总体效果可能是抑制内在和突触介导的活动，并由规则的高频放电取代。
