Parkinson's disease: controlling movement difficulties

The spontaneous electrical activity of dopaminergic neurons enables us to make smooth movements. While it has been shown that the entry of calcium into these neurons renders them vulnerable, several research groups have focused upon the role of calcium channels in the spontaneous electrical activity of dopaminergic neurons. Is it possible to block the entry of calcium in order to preserve these nerve cells, without altering their spontaneous activity? After years of debate, ULg researchers have now contributed to this issue. Their study, which combines mathematical modelling and experiments, is published in PLoS Computational Biology (1).

As basic units of the nervous system, neurons allow us to feel, think, speak, and act through the  impulses which they transmit. The several thousands of billions of nerve cells in our body connect with one another so that we can accomplish complex and precise mental and physical tasks.

However, like any other cell in our body, neurons sometimes become dysfunctional. The consequences of neural dysfunction depends on the type of neuron affected and the scale of the defect.

Parkinson's Disease is an example of an illness linked to neural dysfunction. In this case, it is principally the degeneration of dopaminergic neurons which causes the disease. These neurons are present in the substantia nigra pars compacta and the ventral tegmental area of the brain. Depending on where they are located, dopaminergic neurons are involved in a variety of functions. "In the ventral tegmental area, they play a role in the reward circuitry and in addiction mechanisms" explains Guillaume Drion, a doctoral student in biomedical and pharmaceutical sciences in the GIGA-Neurosciences. "Those located in the substantia nigra pars compacta area,  are involved in movement control", says the young researcher. In the case of Parkinson's Disease, these are the ones which are of interest to researchers.

As their name indicates, dopaminergic neurons produce and release dopamine. This neurotransmitter, according to whether it is present in small or large quantities in the synapse, separating two neurons, will have different effects on the downstream neuron. If little dopamine is released, only receptors which inhibit this neuron will be activated. If a large amount of dopamine is present in the synapse, this neurotransmitter will also bind to the  excitatory receptors of the subsequent neuron. Overall, therefore, dopamine will have an excitatory effect and will lead to the initiation of movement. (Read : Dopamine at the service of movement)

inpact firing

(1) Guillaume Drion, Laurent Massotte, Rodolphe Sepulchre and Vincent Seutin. How Modeling Can Reconcile Apparently Discrepant Experimental Results: The Case of Pacemaking in Dopaminergic Neurons. PLoS Comput Biol, 2011, 7(5): e1002050. doi:10.1371/journal.pcbi.1002050

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