Lee Kendall H, Roberts David W, Kim Uhnoh
Section of Neurosurgery, Dartmouth Medical School, Lebanon, NH, USA.
Stereotact Funct Neurosurg. 2003;80(1-4):32-6. doi: 10.1159/000075157.
BACKGROUND/AIMS: The precise mechanism of action of deep brain stimulation in the subthalamic nucleus (STN) for the treatment of Parkinson's disease and epilepsy is unknown. In the present study, the intracellular effects on STN neurons following high-frequency stimulation (HFS) of STN were examined to test the hypothesis that HFS results in either an increase or a decrease in neuronal action potential generation.
Intracellular electrophysiological recordings were made in the rat STN neurons in in vitro slice preparations. A concentric bipolar stimulating electrode was placed in the STN, and electrical stimulation (duration, 100-2000 ms; amplitude, 10-500 microA, and frequency, 10-200 Hz) was delivered while simultaneously recording intracellularly from a STN neuron using a sharp electrode.
HFS of STN resulted in the generation of excitatory postsynaptic potentials and an increase in action potential firing during the stimulation period followed by a period of poststimulation inhibition of firing in STN neurons. The degree of increase in action potentials from HFS was critically dependent on the frequency of electrical stimulation, i.e. at approximately 100-140 Hz, maximal increase was obtained, but at 200 Hz, the activity was blocked. Interestingly, the duration of poststimulation inhibition of firing was dependent on the duration of stimulation, i.e. the longer the HFS, the longer the inhibition.
These results suggest that the mechanism of action of deep brain stimulation involves initial excitation followed by later inhibition of STN neurons at a cellular level rather than primary inhibition, as previously hypothesized.
背景/目的：丘脑底核（STN）深部脑刺激治疗帕金森病和癫痫的确切作用机制尚不清楚。在本研究中，检测了STN高频刺激（HFS）后对STN神经元的细胞内效应，以验证HFS导致神经元动作电位产生增加或减少这一假说。
在体外脑片制备中对大鼠STN神经元进行细胞内电生理记录。将同心双极刺激电极置于STN，施加电刺激（持续时间100 - 2000毫秒；幅度10 - 500微安，频率10 - 200赫兹），同时使用尖锐电极从一个STN神经元进行细胞内记录。
STN的HFS导致兴奋性突触后电位的产生，并且在刺激期间动作电位发放增加，随后是STN神经元的刺激后发放抑制期。HFS引起的动作电位增加程度关键取决于电刺激频率，即大约在100 - 140赫兹时获得最大增加，但在200赫兹时，活动被阻断。有趣的是，刺激后发放抑制的持续时间取决于刺激的持续时间，即HFS时间越长，抑制时间越长。
这些结果表明，深部脑刺激的作用机制在细胞水平上涉及对STN神经元的初始兴奋，随后是抑制，而不是如先前假设的主要为抑制作用。
