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The Journal of Neurophysiology Vol. 86 No. 1 July 2001, pp. 249-260
Copyright ©2001 by the American Physiological Society
1Department of Physiology, Faculty of Medicine, University of Toronto, Toronto M5S 1A8; and 2Department of Surgery, University of Toronto, Division of Neurosurgery, 3The Toronto Western Research Institute, and 4Department of Medicine, University of Toronto, Division of Neurology, The Toronto Western Hospital, Toronto, Ontario M5T 2S8, Canada
Levy, R.,
J. O. Dostrovsky,
A. E. Lang,
E. Sime,
W. D. Hutchison, and
A.
M. Lozano.
Effects of Apomorphine on Subthalamic Nucleus and Globus Pallidus
Internus Neurons in Patients With Parkinson's Disease. J. Neurophysiol. 86: 249-260, 2001. This
study examines the effect of apomorphine (APO), a nonselective
D1- and D2-dopamine
receptor agonist, on the firing activity of neurons in the subthalamic
nucleus (STN) and internal segment of the globus pallidus (GPi) in
patients with Parkinson's disease (PD). Single-unit microelectrode
recordings were conducted in 13 patients undergoing implantation of
deep brain stimulation electrodes in STN and 6 patients undergoing a
pallidotomy. Doses of APO (2.5-8 mg) were sufficient to produce an
ON state, but not intended to induce dyskinetic movements.
Following baseline recordings from a single neuron, APO was
administered and the activity of the neuron followed for an average of
15 min. The spontaneous discharge of neurons encountered before
(n = 309), during (n = 146, 10-60
min), and after the effect of APO had waned (n = 127, >60 min) was also sampled, and the response to passive joint movements
was noted. In both nuclei, APO increased the overall proportion of
spikes in burst discharges (as detected with Poisson "surprise"
analysis), and a greater proportion of cells with an irregular
discharge pattern was observed. APO significantly decreased the overall
firing rates of GPi neurons (P < 0.01), but there was
no change in the overall firing rate of neurons in the STN (P = 0.68). However, the mean firing rates of STN
neurons during APO-induced movements (choreic or dystonic dyskinesias)
that occurred in four patients were significantly lower than
OFF-period baseline values (P < 0.05).
Concurrent with a reduction in limb tremor, the percentage of cells
with tremor-related activity (TCs) was found to be significantly
reduced from 19 to 6% in the STN and 14 to 0% in the GPi following
APO administration. APO also decreased the firing rate of STN TCs
(P < 0.05). During the OFF state, more than 15% of neurons tested (STN = 93, GPi = 63) responded to
passive movement of two or more joints. After APO, this proportion
decreased significantly to 7% of STN cells and 4% of GPi cells
(STN = 28, GPi = 26). These findings suggest that the
APO-induced amelioration of parkinsonian symptoms is not solely due to
a decrease in overall activity in the GPi or STN as predicted by the
current model of basal ganglia function in PD.
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