Incorrectly synchronized
Movements are controlled by a finely tuned interplay of nerve activity. In the case of shaking paralysis, this attunement apparently collapses and all nerves suddenly fire wildly.
Parkinson's disease turns the simplest of movements into a desperate struggle: hands tremble uncontrollably, it is difficult to even walk or balance, and sometimes muscles become suddenly stiff, causing the patient to fall frozen in motion. Even communication is affected as the words drag out slowly.
The cause of the stalled movements lies in the brain: in the basal ganglia of the midbrain – especially in the substantia nigra – nerve cells that produce dopamine die off. If the messenger substance is missing, the movement control gets out of balance. This is because dopamine regulates the activity of the striatum in the midbrain, which in turn transmits information to the motor cortex in the cerebrum, which ultimately controls movement.
The strong movement disorders of Parkinson's patients probably result from a reduced function of the nerve cells in the motor cortex - at least that's the conventional wisdom. But apparently the total activity of the nerve cells is not reduced at all, but just completely out of step, as Rui Costa from the National Institutes of He alth and Duke University and his team have now discovered.
The scientists worked with genetically modified mice, to which they were able to regulate the amount of dopamine in the brain by administering two substances: If the researchers gave the mutants a substance with the acronym AMPT, which prevents the synthesis of dopamine, the mice lapsed within few minutes in rigidity, from which she could only be freed by the administration of dopamine.
Costa and his colleagues now targeted the work of individual neurons in the striatum and motor cortex. Using ultra-fine electrodes, they tapped into the nerve cells and derived their excitation while alternately injecting AMPT and dopamine into their test animals.
If the dopamine level in the rodent's brain fell drastically as a result of the administration of AMPT, the animals fell into rigidity – as expected. The nervous control system in the brain went completely off track: around seventy percent of the nerves in both the striatum and the motor cortex changed their activity.
In the striatum, most of the nerves just stopped working, and only a small fraction fired harder. In the motor cortex, on the other hand, about half of the neurons became more active, while the other half stopped doing anything. Overall, the nerve activity in this area of the brain remained roughly the same.
If the mice were then injected with dopamine, the activity of practically all nerve cells in both brain areas returned to their respective starting levels, and the animals were also able to move normally again. It was noticeable that all neurons fired synchronously with a lack of dopamine, but with sufficient dopamine they worked asynchronously.
On the basis of their observations, Costa and his colleagues suspect that it is not, as previously assumed, a generally reduced activity of the nerve cells in the motor cortex that causes the movement disorders in Parkinson's disease, but rather a faulty synchronization of the normally asynchronously working nerves responsible for. Therapeutic measures that prevent this synchronization and preserve the normal cooperation of the neurons could potentially help Parkinson's patients achieve fluid movements.
