Involvement of GABAergic pathway on inhibition of subthalamic nucleus high-frequency stimulation of spontaneous firing activity in substantia nigra pars reticulata neurons in a rat model of Parkinson's disease

摘要

BACKGROUND: Subthalamic nucleus-high frequency stimulation (STN-HFS) plays an importantrole in the treatment of Parkinson's disease, but the mechanisms underlying STN-HFS remainunclear. Some studies have demonstrated that STN stimulation inhibits the firing activity ofsubstantia nigra pars reticulata neurons.OBJECTIVE: To investigate the effects of different-frequency STN stimulation andmicroiontophoresis of gamma-aminobutyric acid (GABA) and its antagonist, bicuculline, onspontaneous firing activity in a rat model of Parkinson's disease, and to analyze the action pathwayof high frequency stimulation in firing activity inhibition of substantia nigra pars reticulata neurons.DESIGN, TIME AND SETTING: This neuroelectrophysiological, animal experiment was performedat the Electrophysiology Laboratory of Liaoning Medical University, China from March to August2008.MATERIALS: 6-hydroxydopamine (6-OHDA) (Sigma, USA), A320R isolated stimulus and DAM80preamplifier (World Precision Instruments, USA), 6400A microiontophoresis apparatus (Dagan,USA), and Spike 2 biological signal acquisition system (CED, UK) were used in this study.METHODS: A total of 20 Sprague Dawley rats were used to establish a Parkinson's disease modelvia injection of 6-OHDA into the right striatum. Electrical stimulation (0.06-ms width, 0.4-mA intensity20-200-Hz frequency, 5-second train duration) was delivered to the subthalamic nucleus. Peripheralchannels were separately filled with GABA (pH 3.5, 0.2 mol/L), bicuculline (pH 4.0, 0.01 mol/L), andNaCl (pH 7.0, 3 mol/L). The electrode was positioned with a WK-2 microelectrode propulsion device,and was slowly inserted into the substantia nigra pars reticulata to record spontaneous firing activityof substantia nigra pars reticulata neurons.MAIN OUTCOME MEASURES: The number and firing rate of substantia nigra pars reticulataneurons which were either inhibited or excited were measured.RESULTS: Substantia nigra pars reticulata neurons were inhibited by STN stimulation. Theproportion of inhibited substantia nigra pars reticulata neurons increased with increasing stimulationfrequency. GABA had a tonic inhibitory effect on substantia nigra pars reticulata neurons.Microiontophoresis of bicuculline suppressed the inhibitory effect of STN-HFS on 67% (4/6) ofsubstantia nigra pars reticulata neurons.CONCLUSION: STN-HFS ameliorated abnormal activity in substantia nigra pars reticulata neuronsvia the inhibitory effect of GABA treatment in a rat model of Parkinson's disease.