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- Title
Levodopa enhances synaptic plasticity in the substantia nigra pars reticulata of Parkinsons disease patients.
- Authors
I. A. Prescott; J. O. Dostrovsky; E. Moro; M. Hodaie; A. M. Lozano; W. D. Hutchison
- Abstract
Parkinsons disease, 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 Parkinsons disease 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 Parkinsons disease patients undergoing implantation of deep brain stimulating (DBS) electrodes in the subthalamic nucleus (STN). High frequency stimulation (HFSâfour trains of 2 s at 100 Hz) in the SNr failed to induce a lasting change in test fEPs (1 Hz) amplitudes in patients OFF medication (decayed to baseline by 160 s). Following oral l-dopa administration, HFS induced a potentiation of the fEP amplitudes (.3% of baseline at 160 s 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 Parkinsons disease.
- Subjects
DOPA; PHARMACODYNAMICS; NEUROPLASTICITY; PARKINSON'S disease patients; TREATMENT of neurodegeneration; SUBSTANTIA nigra; ZONA reticularis
- Publication
Brain: A Journal of Neurology, 2009, Vol 132, Issue 2, p309
- ISSN
0006-8950
- Publication type
Article
- DOI
10.1093/brain/awn322