Dopaminergic modulation of synaptic plasticity in the SNr of PD patients
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1
University of Toronto & Toronto Western Research Institute and Krembil Neuroscience Centre, Department of Physiology, Faculty of Medicine, Canada
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2
University of Toronto & Toronto Western Research Institute and Krembil Neuroscience Centre, Department of Surgery, Division of Neurosurgery, Canada
Parkinson’s disease (PD), caused by the loss of dopaminergic nigrostriatal projections, is a debilitating neurodegenerative disease characterized by bradykinesia, rigidity, tremor, and postural instability. The dopamine precursor levodopa (L-Dopa) is the most effective treatment for the amelioration of PD signs and symptoms, but long-term administration can lead to disabling motor fluctuations and L-Dopa-induced dyskinesias (LIDs). Studies in rat striatal slices have shown dopamine to be an essential component of activity-dependent synaptic plasticity at the input to the basal ganglia, but dopamine is also released from ventrally projecting dendrites of the substantia nigra pars compacta (SNc) on the substantia nigra pars reticulata (SNr), a major output structure of the basal ganglia. We characterized synaptic plasticity in the SNr using field potentials evoked with a nearby microelectrode (fEPs), in 18 PD patients undergoing implantation of deep brain stimulating (DBS) electrodes in the subthalamic nucleus (STN). High frequency stimulation (HFS – 4 trains of 2s at 100Hz) in the SNr failed to induce a lasting change in test fEPs (1 Hz) amplitudes in patients OFF medication (decayed to baseline by 160s). Following oral L-Dopa administration, HFS induced a potentiation of the fEP amplitudes (+ 29.3 % of baseline at 160s following a plateau). Our findings suggest that extrastriatal dopamine modulates activity dependent synaptic plasticity at basal ganglia output neurons. Dopamine medication state clearly impacts fEP amplitude, and the lasting nature of the increase is reminiscent of LTP-like changes, indicating that aberrant synaptic plasticity may play a role in the pathophysiology of PD.
(This study was funded by the PSC Pilot Project Grant and CIHR)
Conference:
B.R.A.I.N. platform in Physiology poster day 2009, Toronto, ON, Canada, 16 Dec - 16 Dec, 2009.
Presentation Type:
Oral Presentation
Topic:
Oral presentations
Citation:
Prescott
I,
Dostrovsky
JO,
Hodaie
M,
Lozano
AM and
Hutchison
WD
(2009). Dopaminergic modulation of synaptic plasticity in the SNr of PD patients.
Front. Neurosci.
Conference Abstract:
B.R.A.I.N. platform in Physiology poster day 2009.
doi: 10.3389/conf.neuro.03.2009.17.034
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Received:
17 Dec 2009;
Published Online:
17 Dec 2009.
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Correspondence:
Ian Prescott, University of Toronto & Toronto Western Research Institute and Krembil Neuroscience Centre, Department of Physiology, Faculty of Medicine, Toronto, Canada, ian.prescott@utoronto.ca