The Subthalamic Nucleus becomes a Generator of Bursts in the Dopamine-Depleted State. Its High Frequency Stimulation Dramatically Weakens Transmission to the Globus Pallidus
Open Access
- 1 January 2011
- journal article
- research article
- Published by Frontiers Media SA in Frontiers in Systems Neuroscience
- Vol. 5, 43
- https://doi.org/10.3389/fnsys.2011.00043
Abstract
Excessive burst firing in the dopamine-depleted basal ganglia correlates with severe motor symptoms of Parkinson’s disease that are attenuated by high frequency electrical stimulation of the subthalamic nucleus. Here we test the hypothesis that pathological bursts in dopamine-deprived basal ganglia are generated within the subthalamic nucleus and transmitted to globus pallidus neurons. To answer this question we recorded excitatory synaptic currents and potentials from subthalamic and pallidal neurons in the basal ganglia slice from dopamine-depleted mice while continuously blocking GABAA receptors. In control mice, a single electrical stimulus delivered to the internal capsule or the rostral pole of the subthalamic nucleus evoked a short duration, small amplitude, monosynaptic EPSC in subthalamic neurons. In contrast, in the dopamine-depleted basal ganglia slice, this monosynaptic EPSC was amplified and followed by a burst of polysynaptic EPSCs that eventually reverberated three to seven times, providing a long lasting response that gave rise to bursts of EPSCs and spikes in GP neurons. Repetitive (10 to 120 Hz) stimulation delivered to the subthalamic nucleus in the dopamine-depleted basal ganglia slice attenuated subthalamic nucleus-evoked bursts of EPSCs in pallidal neurons after several minutes of stimulation but only high frequency (90-120 Hz) stimulation replaced them with small amplitude EPSCs at 20 Hz. We propose that the polysynaptic pathway within the subthalamic nucleus amplifies subthalamic responses to incoming excitation in the dopamine-depleted basal ganglia, thereby transforming the subthalamic nucleus into a burst generator and entraining pallidal neurons in pathogenic bursting activities. High frequency stimulation of the subthalamic nucleus prevents the transmission of this pathological activity to globus pallidus and imposes a new glutamatergic synaptic noise on pallidal neurons.Keywords
This publication has 57 references indexed in Scilit:
- Resonance in subthalamo-cortical circuits in Parkinson's diseaseBrain, 2009
- D2‐like dopamine receptor‐mediated modulation of activity‐dependent plasticity at GABAergic synapses in the subthalamic nucleusThe Journal of Physiology, 2008
- Complex EPSCs evoked in substantia nigra reticulata neurons are disrupted by repetitive stimulation of the subthalamic nucleusSynapse, 2008
- Biochemical and electrophysiological changes of substantia nigra pars reticulata driven by subthalamic stimulation in patients with Parkinson's diseaseEuropean Journal of Neuroscience, 2006
- Subthalamic stimulation evokes complex EPSCs in the rat substantia nigra pars reticulata in vitroThe Journal of Physiology, 2006
- Impact of High-Frequency Stimulation Parameters on the Pattern of Discharge of Subthalamic NeuronsJournal of Neurophysiology, 2005
- Neuroleptic-Induced Catalepsy: Electrophysiological Mechanisms of Functional Recovery Induced by High-Frequency Stimulation of the Subthalamic NucleusJournal of Neuroscience, 2005
- Calcium‐dependent subthreshold oscillations determine bursting activity induced by N‐methyl‐d‐aspartate in rat subthalamic neurons in vitroEuropean Journal of Neuroscience, 2004
- The impact of receptor desensitization on fast synaptic transmissionTrends in Neurosciences, 1996
- Excitatory influence of rat subthalamic nucleus to substantia nigra pars reticulata and the pallidal complex: electrophysiological dataBrain Research, 1990