Neurotransmitter release from high-frequency stimulation of the subthalamic nucleus

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Object. High-frequency stimulation (HFS) delivered through implanted electrodes in the subthalamic nucleus (STN) has become an established treatment for Parkinson disease (PD). The precise mechanism of action of deep brain stimulation (DBS) in the STN is unknown, however. In the present study, the authors tested the hypothesis that HFS within the STN changes neuronal action potential firing rates during the stimulation period by modifying neurotransmitter release.

Methods. Intracellular electrophysiological recordings were obtained using sharp electrodes in rat STN neurons in an in vitro slice preparation. A concentric bipolar stimulating electrode was placed in the STN slice, and electrical stimulation (pulse width 50–100 µsec, duration 100–2000 µsec, amplitude 10–500 µA, and frequency 10–200 Hz) was delivered while simultaneously obtaining intracellular recordings from an STN neuron.

High-frequency stimulation of the STN either generated excitatory postsynaptic potentials (EPSPs) and increased the action potential frequency or it generated inhibitory postsynaptic potentials and decreased the action potential frequency of neurons within the STN. These effects were blocked after antagonists to glutamate and γ-aminobutyric acid were applied to the tissue slice, indicating that HFS resulted in the release of neurotransmitters. Intracellular recordings from substantia nigra pars compacta (SNc) dopaminergic neurons during HFS of the STN revealed increased generation of EPSPs and increased frequency of action potentials in SNc neurons.

Conclusions. During HFS of STN neurons the mechanism of DBS may involve the release of neurotransmitters rather than the primary electrogenic inhibition of neurons.

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Figures

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    Tracings obtained during an extracellular multiunit recording from the STN, revealing poststimulus inhibition of action potential generation. A single 10-second duration electrical stimulus at 100 Hz delivered within approximately 200 µm from the STN recording electrode produced a stimulation artifact, followed by the inhibition of neuronal firing lasting approximately 30 seconds and the gradual return of spontaneous activity. Due to the stimulation artifact, it was impossible to see what happened during stimulation.

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    a: Tracing of an intracellular recording from an STN neuron revealing that electrical stimulation could generate action potentials at 53 to 78 Hz during the stimulation period. At the end of stimulation, there was an inhibition of neuronal firing lasting 1.8 seconds. b: Tracing demonstrating that the membrane potential of the STN neuron was held at −80 mV with the intracellular injection of hyperpolarizing direct current. A single electrical stimulus applied at 10 Hz resulted in the generation of subthreshold EPSPs. c: Magnification of segment featured in b. d: Tracing obtained by increasing the stimulation frequency to 20 Hz, revealing the frequency-dependent summation of EPSPs such that, even at −80 mV membrane-holding potential, stimulation was able to generate action potentials. e: Magnification of segment featured in d. f: Tracing obtained in another STN neuron, revealing that 20-Hz stimulation resulted in IPSPs and blockage of action potential generation. g: Magnification of segment featured in f.

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    Tracings obtained during electrical stimulation (100 Hz frequency) in the continuous presence of glutamate and GABA receptor antagonists, showing complete blockage of the postsynaptic potentials.

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    Intracellular recordings obtained from a SNc neuron. Upper: High-frequency stimulation of the STN resulting in the generation of EPSPs and action potentials. Lower: Magnification of portion featured in the upper panel.

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    Tracings of membrane responses to various frequencies of electrical stimulation. The cell was held at its resting potential of −60mV and various frequencies (20–200 Hz) of stimulation were applied. a: At 20–140 Hz stimulation, the cell increased its firing frequency, followed by a period of inhibition during poststimulation. Interestingly, at 200 Hz the ability of the cell to fire action potentials was blocked. b: Magnification of portion featured in a. c: Magnification of portion featured in b. d: Graph of stimulation frequency compared with frequency of action potential generation. Maximal firing was induced at approximately 100 Hz stimulation.

References

  • 1.

    Abosch AKapur SLang AEet al: Stimulation of the subthalamic nucleus in Parkinson's disease does not produce striatal dopamine release. Neurosurgery 53:109511052003Abosch A Kapur S Lang AE et al: Stimulation of the subthalamic nucleus in Parkinson's disease does not produce striatal dopamine release. Neurosurgery 53:1095–1105 2003

    • Search Google Scholar
    • Export Citation
  • 2.

    Aghajanian GKRasmussen K: Intracellular studies in the facial nucleus illustrating a simple new method for obtaining viable motoneurons in adult rat brain slices. Synapse 3:3313381989Aghajanian GK Rasmussen K: Intracellular studies in the facial nucleus illustrating a simple new method for obtaining viable motoneurons in adult rat brain slices. Synapse 3:331–338 1989

    • Search Google Scholar
    • Export Citation
  • 3.

    Benabid ALPollak PGross Cet al: Acute and long-term effects of subthalamic nucleus stimulation in Parkinson's disease. Stereotact Funct Neurosurg 62:76841994Benabid AL Pollak P Gross C et al: Acute and long-term effects of subthalamic nucleus stimulation in Parkinson's disease. Stereotact Funct Neurosurg 62:76–84 1994

    • Search Google Scholar
    • Export Citation
  • 4.

    Benazzouz AGao DNi Zet al: High frequency stimulation of the STN influences the activity of dopamine neurons in the rat. Neuroreport 11:159315962000Benazzouz A Gao D Ni Z et al: High frequency stimulation of the STN influences the activity of dopamine neurons in the rat. Neuroreport 11:1593–1596 2000

    • Search Google Scholar
    • Export Citation
  • 5.

    Benazzouz AGross CFeger Jet al: Reversal of rigidity and improvement in motor performance by subthalamic high-frequency stimulation in MPTP-treated monkeys. Eur J Neurosci 5:3823891993Benazzouz A Gross C Feger J et al: Reversal of rigidity and improvement in motor performance by subthalamic high-frequency stimulation in MPTP-treated monkeys. Eur J Neurosci 5:382–389 1993

    • Search Google Scholar
    • Export Citation
  • 6.

    Benazzouz APiallat BPollak Pet al: Responses of substantia nigra pars reticulata and globus pallidus complex to high frequency stimulation of the subthalamic nucleus in rats: electrophysiological data. Neurosci Lett 189:77801995Benazzouz A Piallat B Pollak P et al: Responses of substantia nigra pars reticulata and globus pallidus complex to high frequency stimulation of the subthalamic nucleus in rats: electrophysiological data. Neurosci Lett 189:77–80 1995

    • Search Google Scholar
    • Export Citation
  • 7.

    Beurrier CBioulac BAudin Jet al: High-frequency stimulation produces a transient blockade of voltage-gated currents in subthalamic neurons. J Neurophysiol 85:135113562001Beurrier C Bioulac B Audin J et al: High-frequency stimulation produces a transient blockade of voltage-gated currents in subthalamic neurons. J Neurophysiol 85:1351–1356 2001

    • Search Google Scholar
    • Export Citation
  • 8.

    Blaha CDAllen LFDas Set al: Modulation of dopamine efflux in the nucleus accumbens after cholinergic stimulation of the ventral tegmental area in intact, pedunculopontine tegmental nucleus-lesioned, and laterodorsal tegmental nucleus-lesioned rats. J Neurosci 16:7147221996Blaha CD Allen LF Das S et al: Modulation of dopamine efflux in the nucleus accumbens after cholinergic stimulation of the ventral tegmental area in intact pedunculopontine tegmental nucleus-lesioned and laterodorsal tegmental nucleus-lesioned rats. J Neurosci 16:714–722 1996

    • Search Google Scholar
    • Export Citation
  • 9.

    Blaha CDLane RF: Direct in vivo electrochemical monitoring of dopamine release in response to neuroleptic drugs. Eur J Pharmacol 98:1131171984Blaha CD Lane RF: Direct in vivo electrochemical monitoring of dopamine release in response to neuroleptic drugs. Eur J Pharmacol 98:113–117 1984

    • Search Google Scholar
    • Export Citation
  • 10.

    Blaha CDPhillips AG: Application of in vivo electrochemistry to the measurement of changes in dopamine release during intracranial self-stimulation. J Neurosci Methods 34:1251331990Blaha CD Phillips AG: Application of in vivo electrochemistry to the measurement of changes in dopamine release during intracranial self-stimulation. J Neurosci Methods 34:125–133 1990

    • Search Google Scholar
    • Export Citation
  • 11.

    Bruet NWindels FBertrand Aet al: High frequency stimulation of the subthalamic nucleus increases the extracellular contents of striatal dopamine in normal and partially dopaminergic denervated rats. J Neuropathol Exp Neurol 60:15242001Bruet N Windels F Bertrand A et al: High frequency stimulation of the subthalamic nucleus increases the extracellular contents of striatal dopamine in normal and partially dopaminergic denervated rats. J Neuropathol Exp Neurol 60:15–24 2001

    • Search Google Scholar
    • Export Citation
  • 12.

    Chergui KSuaud-Chagny MFGonon F: Nonlinear relationship between impulse flow, dopamine release and dopamine elimination in the rat brain in vivo. Neuroscience 62:6416451994Chergui K Suaud-Chagny MF Gonon F: Nonlinear relationship between impulse flow dopamine release and dopamine elimination in the rat brain in vivo. Neuroscience 62:641–645 1994

    • Search Google Scholar
    • Export Citation
  • 13.

    The Deep-Brain Stimulation for Parkinson's Disease Study Group: Deep-brain stimulation of the subthalamic nucleus or the pars interna of the globus pallidus in Parkinson's disease. N Engl J Med 345:9569632001The Deep-Brain Stimulation for Parkinson's Disease Study Group: Deep-brain stimulation of the subthalamic nucleus or the pars interna of the globus pallidus in Parkinson's disease. N Engl J Med 345:956–963 2001

    • Search Google Scholar
    • Export Citation
  • 14.

    Dostrovsky JOLozano AM: Mechanisms of deep brain stimulation. Mov Disord 17 (Suppl 3):S63S682002Dostrovsky JO Lozano AM: Mechanisms of deep brain stimulation. Mov Disord 17 (Suppl 3):S63–S68 2002

    • Search Google Scholar
    • Export Citation
  • 15.

    Dugast CSuaud-Chagny MFGonon F: Continuous in vivo monitoring of evoked dopamine release in the rat nucleus accumbens by amperometry. Neuroscience 62:6476541994Dugast C Suaud-Chagny MF Gonon F: Continuous in vivo monitoring of evoked dopamine release in the rat nucleus accumbens by amperometry. Neuroscience 62:647–654 1994

    • Search Google Scholar
    • Export Citation
  • 16.

    Forster GLBlaha CD: Pedunculopontine tegmental stimulation evokes striatal dopamine efflux by activation of acetylcholine and glutamate receptors in the midbrain and pons of the rat. Eur J Neurosci 17:7517622003Forster GL Blaha CD: Pedunculopontine tegmental stimulation evokes striatal dopamine efflux by activation of acetylcholine and glutamate receptors in the midbrain and pons of the rat. Eur J Neurosci 17:751–762 2003

    • Search Google Scholar
    • Export Citation
  • 17.

    Fujimoto KKita H: Response characteristics of subthalamic neurons to the stimulation of the sensorimotor cortex in the rat. Brain Res 609:1851921993Fujimoto K Kita H: Response characteristics of subthalamic neurons to the stimulation of the sensorimotor cortex in the rat. Brain Res 609:185–192 1993

    • Search Google Scholar
    • Export Citation
  • 18.

    Garcia LAudin JD'Alessandro Get al: Dual effect of high-frequency stimulation on subthalamic neuron activity. J Neurosci 23:874387512003Garcia L Audin J D'Alessandro G et al: Dual effect of high-frequency stimulation on subthalamic neuron activity. J Neurosci 23:8743–8751 2003

    • Search Google Scholar
    • Export Citation
  • 19.

    Hammond CDeniau JMRizk Aet al: Electrophysiological demonstration of an excitatory subthalamonigral pathway in the rat. Brain Res 151:2352441978Hammond C Deniau JM Rizk A et al: Electrophysiological demonstration of an excitatory subthalamonigral pathway in the rat. Brain Res 151:235–244 1978

    • Search Google Scholar
    • Export Citation
  • 20.

    Hashimoto TElder CMOkun MSet al: Stimulation of the subthalamic nucleus changes the firing pattern of pallidal neurons. J Neurosci 23:191619232003Hashimoto T Elder CM Okun MS et al: Stimulation of the subthalamic nucleus changes the firing pattern of pallidal neurons. J Neurosci 23:1916–1923 2003

    • Search Google Scholar
    • Export Citation
  • 21.

    Kang YFutami T: Arrhythmic firing in dopamine neurons of rat substantia nigra evoked by activation of subthalamic neurons. J Neurophysiol 82:163216371999Kang Y Futami T: Arrhythmic firing in dopamine neurons of rat substantia nigra evoked by activation of subthalamic neurons. J Neurophysiol 82:1632–1637 1999

    • Search Google Scholar
    • Export Citation
  • 22.

    Kita HChang HTKitai ST: Pallidal inputs to subthalamus: intracellular analysis. Brain Res 264:2552651983Kita H Chang HT Kitai ST: Pallidal inputs to subthalamus: intracellular analysis. Brain Res 264:255–265 1983

    • Search Google Scholar
    • Export Citation
  • 23.

    Kita HKitai ST: Efferent projections of the subthalamic nucleus in the rat: light and electron microscopic analysis with the PHA-L method. J Comp Neurol 260:4354521987Kita H Kitai ST: Efferent projections of the subthalamic nucleus in the rat: light and electron microscopic analysis with the PHA-L method. J Comp Neurol 260:435–452 1987

    • Search Google Scholar
    • Export Citation
  • 24.

    Kolomiets BPDeniau JMMailly Pet al: Segregation and convergence of information flow through the cortico-subthalamic pathways. J Neurosci 21:576457722001Kolomiets BP Deniau JM Mailly P et al: Segregation and convergence of information flow through the cortico-subthalamic pathways. J Neurosci 21:5764–5772 2001

    • Search Google Scholar
    • Export Citation
  • 25.

    Krack PBatir AVan Blercom Net al: Five-year follow-up of bilateral stimulation of the subthalamic nucleus in advanced Parkinson's disease. N Engl J Med 349:192519342003Krack P Batir A Van Blercom N et al: Five-year follow-up of bilateral stimulation of the subthalamic nucleus in advanced Parkinson's disease. N Engl J Med 349:1925–1934 2003

    • Search Google Scholar
    • Export Citation
  • 26.

    Limousin PKrack PPollak Pet al: Electrical stimulation of the subthalamic nucleus in advanced Parkinson's disease. N Engl J Med 339:110511111998Limousin P Krack P Pollak P et al: Electrical stimulation of the subthalamic nucleus in advanced Parkinson's disease. N Engl J Med 339:1105–1111 1998

    • Search Google Scholar
    • Export Citation
  • 27.

    Lozano AMDostrovsky JChen Ret al: Deep brain stimulation for Parkinson's disease: disrupting the disruption. Lancet Neurol 1:2252312002Lozano AM Dostrovsky J Chen R et al: Deep brain stimulation for Parkinson's disease: disrupting the disruption. Lancet Neurol 1:225–231 2002

    • Search Google Scholar
    • Export Citation
  • 28.

    Magarinos-Ascone CPazo JHMacadar Oet al: High-frequency stimulation of the subthalamic nucleus silences subthalamic neurons: a possible cellular mechanism in Parkinson's disease. Neuroscience 115:110911172002Magarinos-Ascone C Pazo JH Macadar O et al: High-frequency stimulation of the subthalamic nucleus silences subthalamic neurons: a possible cellular mechanism in Parkinson's disease. Neuroscience 115:1109–1117 2002

    • Search Google Scholar
    • Export Citation
  • 29.

    Maurice NDeniau JMGlowinski Jet al: Relationships between the prefrontal cortex and the basal ganglia in the rat: physiology of the corticosubthalamic circuits. J Neurosci 18:953995461998Maurice N Deniau JM Glowinski J et al: Relationships between the prefrontal cortex and the basal ganglia in the rat: physiology of the corticosubthalamic circuits. J Neurosci 18:9539–9546 1998

    • Search Google Scholar
    • Export Citation
  • 30.

    Maurice NThierry AMGlowinski Jet al: Spontaneous and evoked activity of substantia nigra pars reticulata neurons during high-frequency stimulation of the subthalamic nucleus. J Neurosci 23:992999362003Maurice N Thierry AM Glowinski J et al: Spontaneous and evoked activity of substantia nigra pars reticulata neurons during high-frequency stimulation of the subthalamic nucleus. J Neurosci 23:9929–9936 2003

    • Search Google Scholar
    • Export Citation
  • 31.

    Meissner WReum TPaul Get al: Striatal dopaminergic metabolism is increased by deep brain stimulation of the subthalamic nucleus in 6-hydroxydopamine lesioned rats. Neurosci Lett 303:1651682001Meissner W Reum T Paul G et al: Striatal dopaminergic metabolism is increased by deep brain stimulation of the subthalamic nucleus in 6-hydroxydopamine lesioned rats. Neurosci Lett 303:165–168 2001

    • Search Google Scholar
    • Export Citation
  • 32.

    Mintz IHammond CGuibert Bet al: Stimulation of the subthalamic nucleus enhances the release of dopamine in the rat substantia nigra. Brain Res 376:4064081986Mintz I Hammond C Guibert B et al: Stimulation of the subthalamic nucleus enhances the release of dopamine in the rat substantia nigra. Brain Res 376:406–408 1986

    • Search Google Scholar
    • Export Citation
  • 33.

    Molinuevo JLValldeoriola FTolosa Eet al: Levodopa withdrawal after bilateral subthalamic nucleus stimulation in advanced Parkinson disease. Arch Neurol 57:9839882000Molinuevo JL Valldeoriola F Tolosa E et al: Levodopa withdrawal after bilateral subthalamic nucleus stimulation in advanced Parkinson disease. Arch Neurol 57:983–988 2000

    • Search Google Scholar
    • Export Citation
  • 34.

    Nambu ATokuno HHamada Iet al: Excitatory cortical inputs to pallidal neurons via the subthalamic nucleus in the monkey. J Neurophysiol 84:2893002000Nambu A Tokuno H Hamada I et al: Excitatory cortical inputs to pallidal neurons via the subthalamic nucleus in the monkey. J Neurophysiol 84:289–300 2000

    • Search Google Scholar
    • Export Citation
  • 35.

    Obeso JARodriguez-Oroz MCRodriguez Met al: Pathophysiologic basis of surgery for Parkinson's disease. Neurology 55 (Suppl 6):S7S122000Obeso JA Rodriguez-Oroz MC Rodriguez M et al: Pathophysiologic basis of surgery for Parkinson's disease. Neurology 55 (Suppl 6):S7–S12 2000

    • Search Google Scholar
    • Export Citation
  • 36.

    Paul GReum TMeissner Wet al: High frequency stimulation of the subthalamic nucleus influences striatal dopaminergic metabolism in the naive rat. Neuroreport 11:4414442000Paul G Reum T Meissner W et al: High frequency stimulation of the subthalamic nucleus influences striatal dopaminergic metabolism in the naive rat. Neuroreport 11:441–444 2000

    • Search Google Scholar
    • Export Citation
  • 37.

    Prensa LCossette MParent A: Dopaminergic innervation of human basal ganglia. J Chem Neuroanat 20:2072132000Prensa L Cossette M Parent A: Dopaminergic innervation of human basal ganglia. J Chem Neuroanat 20:207–213 2000

    • Search Google Scholar
    • Export Citation
  • 38.

    Rizzone MLanotte MBergamasco Bet al: Deep brain stimulation of the subthalamic nucleus in Parkinson's disease: effects of variation in stimulation parameters. J Neurol Neurosurg Psychiatry 71:2152192001Rizzone M Lanotte M Bergamasco B et al: Deep brain stimulation of the subthalamic nucleus in Parkinson's disease: effects of variation in stimulation parameters. J Neurol Neurosurg Psychiatry 71:215–219 2001

    • Search Google Scholar
    • Export Citation
  • 39.

    Robledo PFeger J: Excitatory influence of rat subthalamic nucleus to substantia nigra pars reticulata and the pallidal complex: electrophysiological data. Brain Res 518:47541990Robledo P Feger J: Excitatory influence of rat subthalamic nucleus to substantia nigra pars reticulata and the pallidal complex: electrophysiological data. Brain Res 518:47–54 1990

    • Search Google Scholar
    • Export Citation
  • 40.

    Rouzaire-Dubois BScarnati E: Bilateral corticosubthalamic nucleus projections: an electrophysiological study in rats with chronic cerebral lesions. Neuroscience 15:69791985Rouzaire-Dubois B Scarnati E: Bilateral corticosubthalamic nucleus projections: an electrophysiological study in rats with chronic cerebral lesions. Neuroscience 15:69–79 1985

    • Search Google Scholar
    • Export Citation
  • 41.

    Saint-Cyr JAHoque TPereira LCet al: Localization of clinically effective stimulating electrodes in the human subthalamic nucleus on magnetic resonance imaging. J Neurosurg 97:115211662002Saint-Cyr JA Hoque T Pereira LC et al: Localization of clinically effective stimulating electrodes in the human subthalamic nucleus on magnetic resonance imaging. J Neurosurg 97:1152–1166 2002

    • Search Google Scholar
    • Export Citation
  • 42.

    Salin PManrique CForni Cet al: High-frequency stimulation of the subthalamic nucleus selectively reverses dopamine denervation-induced cellular defects in the output structures of the basal ganglia in the rat. J Neurosci 22:513751482002Salin P Manrique C Forni C et al: High-frequency stimulation of the subthalamic nucleus selectively reverses dopamine denervation-induced cellular defects in the output structures of the basal ganglia in the rat. J Neurosci 22:5137–5148 2002

    • Search Google Scholar
    • Export Citation
  • 43.

    Sato FParent MLevesque Met al: Axonal branching pattern of neurons of the subthalamic nucleus in primates. J Comp Neurol 424:1421522000Sato F Parent M Levesque M et al: Axonal branching pattern of neurons of the subthalamic nucleus in primates. J Comp Neurol 424:142–152 2000

    • Search Google Scholar
    • Export Citation
  • 44.

    Schonfuss DReum TOlshausen Pet al: Modelling constant potential amperometry for investigations of dopaminergic neurotransmission kinetics in vivo. J Neurosci Methods 112:1631722001Schonfuss D Reum T Olshausen P et al: Modelling constant potential amperometry for investigations of dopaminergic neurotransmission kinetics in vivo. J Neurosci Methods 112:163–172 2001

    • Search Google Scholar
    • Export Citation
  • 45.

    Smith IDGrace AA: Role of the subthalamic nucleus in the regulation of nigral dopamine neuron activity. Synapse 12:2873031992Smith ID Grace AA: Role of the subthalamic nucleus in the regulation of nigral dopamine neuron activity. Synapse 12:287–303 1992

    • Search Google Scholar
    • Export Citation
  • 46.

    Suaud-Chagny MFBrun PBuda Met al: Fast in vivo monitoring of electrically evoked dopamine release by differential pulse amperometry with untreated carbon fiber electrodes. J Neurosci Methods 45:1831901992Suaud-Chagny MF Brun P Buda M et al: Fast in vivo monitoring of electrically evoked dopamine release by differential pulse amperometry with untreated carbon fiber electrodes. J Neurosci Methods 45:183–190 1992

    • Search Google Scholar
    • Export Citation
  • 47.

    Suaud-Chagny MFDugast CChergui Ket al: Uptake of dopamine released by impulse flow in the rat mesolimbic and striatal systems in vivo. J Neurochem 65:260326111995Suaud-Chagny MF Dugast C Chergui K et al: Uptake of dopamine released by impulse flow in the rat mesolimbic and striatal systems in vivo. J Neurochem 65:2603–2611 1995

    • Search Google Scholar
    • Export Citation
  • 48.

    Van Der Kooy DHattori T: Single subthalamic nucleus neurons project to both the globus pallidus and substantia nigra in rat. J Comp Neurol 192:7517681980Van Der Kooy D Hattori T: Single subthalamic nucleus neurons project to both the globus pallidus and substantia nigra in rat. J Comp Neurol 192:751–768 1980

    • Search Google Scholar
    • Export Citation
  • 49.

    Voges JVolkmann JAllert Net al: Bilateral high-frequency stimulation in the subthalamic nucleus for the treatment of Parkinson disease: correlation of therapeutic effect with anatomical electrode position. J Neurosurg 96:2692792002Voges J Volkmann J Allert N et al: Bilateral high-frequency stimulation in the subthalamic nucleus for the treatment of Parkinson disease: correlation of therapeutic effect with anatomical electrode position. J Neurosurg 96:269–279 2002

    • Search Google Scholar
    • Export Citation
  • 50.

    Windels FBruet NPoupard Aet al: Effects of high frequency stimulation of subthalamic nucleus on extracellular glutamate and GABA in substantia nigra and globus pallidus in the normal rat. Eur J Neurosci 12:414141462000Windels F Bruet N Poupard A et al: Effects of high frequency stimulation of subthalamic nucleus on extracellular glutamate and GABA in substantia nigra and globus pallidus in the normal rat. Eur J Neurosci 12:4141–4146 2000

    • Search Google Scholar
    • Export Citation

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