Synchronous Oscillations in the Basal-Ganglia-Cortical Network: Do They Generate Tremor and Other Symptoms of Parkinson's Disease?

The main manifestations of Parkinson's disease (PD) are akinesia (poverty of spontaneous movements and difficulty in initiating a movement), bradykinesia (slowness of movement), muscle rigidity and a tremor of 4-7 Hz. The two major subtypes of the human disease present the akinetic/rigid symptoms with and without tremor (tremor dominant vs. akinetic/rigid dominant subtype, respectively). The major cellular event leading to PD is the death of midbrain dopaminergic neurons, resulting in dopamine depletion in the striatum, the input nuclei of the basal ganglia (BG). PD can be investigated using its primate model – MPTP treated monkeys – in which dopaminergic neurons are destroyed by the neurotoxin MPTP. As a result, the monkeys develop motor symptoms similar to those seen in PD patients. Interestingly, monkeys develop the Parkinsonian tremor as a function of their species – African green (vervet) monkeys tend toward tremor, while macaques do not. Recordings from the globus pallidus (GP) and other BG nuclei in MPTP treated monkeys as well as in human patients have shown that Parkinsonian symptoms are accompanied by the appearance of periodic oscillations of neuronal activity. The frequency of these oscillations ranges from 4 to 15 Hz, but their relationship to tremor or other Parkinsonian symptoms is still under debate. Intuitively, tremor is considered to be the result of the low-frequency (4-7 Hz) oscillations. However, this conjecture has not been validated and has even been challenged by several studies. In my study, I attempted to elucidate the connection between Parkinsonian symptoms and neuronal activity in the