Enhanced Synchrony among Primary Motor Cortex Neurons in the 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine Primate Model of Parkinson’s Disease
J. Neurosci.. 2002-06-01; 22(11): 4639-4653
DOI: 10.1523/jneurosci.22-11-04639.2002
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Goldberg JA(1), Boraud T, Maraton S, Haber SN, Vaadia E, Bergman H.
Author information:
(1)Department of Physiology, The Hebrew University-Hadassah Medical School, the
Interdisciplinary Center for Neural Computation, The Hebrew University,
Jerusalem 91120, Israel.
Primary motor cortex (MI) neurons discharge vigorously during voluntary
movement. A cardinal symptom of Parkinson’s disease (PD) is poverty of movement
(akinesia). Current models of PD thus hypothesize that increased inhibitory
pallidal output reduces firing rates in frontal cortex, including MI, resulting
in akinesia and muscle rigidity. We recorded the simultaneous spontaneous
discharge of several neurons in the arm-related area of MI of two monkeys and in
the globus pallidus (GP) of one of the two. Accelerometers were fastened to the
forelimbs to detect movement, and surface electromyograms were recorded from the
contralateral arm of one monkey. The recordings were conducted before and after
systemic treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP),
rendering the animals severely akinetic and rigid with little or no tremor. The
mean spontaneous MI rates during periods of immobility (four to five spikes/sec)
did not change after MPTP; however, in this parkinsonian state, MI neurons
discharged in long bursts (sometimes >2 sec long). These bursts were
synchronized across many cells but failed to elicit detectable movement,
indicating that even robust synchronous MI discharge need not result in
movement. These synchronized population bursts were absent from the GP and were
on a larger timescale than oscillatory synchrony found in the GP of tremulous
MPTP primates, suggesting that MI parkinsonian synchrony arises independently of
basal ganglia dynamics. After MPTP, MI neurons responded more vigorously and
with less specificity to passive limb movement. Abnormal MI firing patterns and
synchronization, rather than reduced firing rates, may underlie PD akinesia and
persistent muscle rigidity.