| Abstract No.: | C-C3097 |
| Country: | Canada |
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| Title: | DOPAMINERGIC MODULATION OF SYNAPTIC PLASTICITY IN THE SNR OF PD PATIENTS |
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| Authors/Affiliations: | 1 Ian Prescott*; 1 Jonathan Dostrovsky; 2 Mojgan Hodaie; 2 Andres Lozano; 1 William Hutchison;
1 Department of Physiology, Faculty of Medicine, University of Toronto; 2 Department of Surgery, Division of Neurosurgery, University of Toronto & Toronto Western Research Institute, ON, Canada
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| Content: | Objectives
The two objectives of this study are: i) to determine the nature of the positive field evoked potential (fEP) we observe in substantia nigra pars reticulata (SNr) recordings, and ii) to determine the relationship between synaptic plasticity in Parkinson’s disease (PD) patients ON and OFF dopaminergic medication.
Materials and Methods
Recordings were performed with 2 independently driven tungsten microelectrodes (15-25um tip, ~1mm separation) during functional stereotactic surgery for the bilateral implantation of chronic electrodes for deep brain stimulation in the subthalamic nucleus (STN) of PD patients. Microstimulation was performed from one electrode while recording the averaged fEP (10 sweeps at 1 Hz, 0.3ms pulse width, 100ua) from the other electrode. To determine the nature of the fEP, SNr neuronal firing was examined during fEPs, paired pulses were made at 20–500ms intervals, and the dorsoventral extent of the +ive field in SNr was measured. Depth profiles were obtained from recordings of the averaged fEP at 250um increments below the stimulation site at the dorsal SNr border. To determine the effects of dopamine on fEP peak amplitudes in SNr, high frequency stimulation (HFS: 2s train, 100Hz, 100ua, repeated 4 times at 10s intervals) was delivered through the stimulating electrode and test fEPs resumed at 1Hz for up to 5mins. The decay time course of fEP peak amplitudes were fitted with an exponential function and time constants (tau) and plateau values (yo) of fEPs were determined for SNr experiments 12hrs off medication and 20min after administration of 100-200mg of L-Dopa (Sinemet). L-Dopa effects were assessed according to the Unified Parkinson’s Disease Rating Scale (UPDRS) as well as patient’s rating of ON state during the procedure.
Results
The fEP occurred during maximal inhibition of the SNr cells with a latency of 5-8ms. Paired pulse depression was observed at 20 and 50ms. The SNr positive field persisted for a depth of approximately 2 mm dorsoventrally. The tau value for the OFF group was 26s and for the ON group was 53s. The plateau value was 103% of baseline (t=1.9, d.f. 153, nsd, n=11) in the OFF group, while the ON group had a plateau at 129% of baseline (t=16.5, d.f. 250, p<0.005, n=10). Averaged UPDRS for the OFF group was 38.1 while for the ON group was 18.9 (lower = less motor deficit).
Conclusion
The fEP is likely a GABA-mediated field IPSP. 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 underlie the pathophysiology of PD.
Support by PSC Pilot Project Grant and CIHR
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