Parkinson's disease: controlling movement difficulties
8/4/11

Tremors, controlled by spontaneous electrical activity.

In order for dopamine to be released by a dopaminergic neuron, the neuron has to be electrically active. Following a stimulus, the ions which are naturally located outside and inside neurons will go from one side of the neuronal membrane to another and trigger the appearance of an action potential, called a "nervous impulse". This spreads along the axon. When it invades the terminal of a neuron, a neurotransmitter is released. It is this chemical message that has an impact on the excitability of the subsequent neuron. Information is thus transmitted from one neuron to another.

While the electrical activity of most neurons appears following a stimulus, dopaminergic neurons exhibit spontaneous electrical activity. "Even when there is no stimulus, production of action potentials by these neurons can be observed" indicates Guillaume Drion. "It is this spontaneous electrical activity which allows us to make smooth movements" he continues. When a significant percentage of dopaminergic neurons degenerate, the production of dopamine becomes insignificant and can no longer finely control movement, hence the appearance of tremors and slowness of movement, and sometimes even the inability to initiate movement. This is the problem we see in patients suffering from Parkinson's Disease. Why do some people's dopaminergic neurons deteriorate? How can this be counteracted? In order to find out, it is necessary to study, in depth, the electrical activity of dopaminergic neurons and, more specifically, their spontaneous electrical activity.

Activity substantia nigra
Calcium - friend or foe?

In the context of his doctoral studies, and under the supervision of his advisors Rodolphe Sepulchre and Vincent Seutin, Guillaume Drion looked at the effect of the entry of calcium ions into dopaminergic neurons during spontaneous electrical activity. "Research groups have realised that the entry of calcium may render dopaminergic neurons vulnerable", explains the PhD student. When calcium enters into the nerve cell, it plays a signalling role, thus triggering other reactions in a domino effect. "But the cell cannot store large quantities of calcium in its cytoplasm, or it will die" specifies Guillaume Drion. "Each calcium entry requires neuronal energy in order to reduce the cytoplasmic concentration of Ca. The more Ca enters, the more neuronal energy is required to pump the calcium towards its reservoirs or outside the cel. This puts a stress on the cell" says the researcher. If the neuron's metabolism is insufficient to meet the energy demand to store the Ca, the neuron degenerates.

Scientists have therefore focused on the following question: can we prevent the deterioration of dopaminergic neurons by blocking the calcium channels used by calcium to enter the cells?"This question has been studied for more than 17 years, but experimental observations have shown  contradictory results" says Guillaume Drion. Some studies have concluded that blocking the calcium channels stops spontaneous electrical activity of the dopaminergic neurons, which would prevents them from producing a constant quantity of dopamine required to control movement. Other studies have come to the opposite conclusion; namely that blocking calcium channels has no effect on the spontaneous electrical activity of these nerve cells.

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