Pathway To Parkinson's Disease Broken DownMain Category: Neurology / Neuroscience
Also Included In: Parkinson's Disease
Article Date: 13 Mar 2013
The number one telltale sign of Parkinson's disease is the breakdown of movement caused by a decrease in the supply of dopamine to the brain region that deals with controlling movement. Exactly how this loss of dopamine in brain cells is affected by Parkinson's disease is outlined in a new study by MIT.
The findings, which are published in the Journal of Neuroscience, detail exact impairments caused by the loss of dopamine and how treatments can be developed to target them.
Ann Graybiel, an MIT Institute Professor and member of MIT's McGovern Institute for Brain Research said:
"We know the neurotransmitter, we know roughly the pathways in the brain that are being affected, but when you come right down to it and ask what exactly is the sequence of events that occurs in the brain, that gets a little tougher."
The Elimination of DopamineThose neurons that control movement are found in a part of the brain called the striatum - which gets information from two large areas - the neocortex and a small region called the substantia nigra.
The job of the cortex is to send sensory information and blueprints for future action, while the substantia nigra sends dopamine that aids in controlling all cortical input.
"This dopamine somehow modulates the circuit interactions in such a way that we don't move too much, we don't move too little, we don't move too fast or too slow, and we don't get overly repetitive in the movements that we make. We're just right."
Parkinson's disease evolves when the neurons linking the substantia nigra to the striatum die - eliminating an essential source of dopamine. Not much is known about this process, however, it is known that not enough dopamine results in movement problems.
A typical treatment for a Parkinson's disease patient includes L-dopa - a substitute for the lost dopamine. However, this therapy normally stops working after five to ten years, and the symptoms worsen.
In an effort to analyze how dopamine loss affects the striatum, the investigators disabled dopamine-releasing cells on one side of the striatum - using rats. This can imitate the starting stages of Parkinson's - when dopamine is eliminated on just one side of the brain.
The researchers documented the electrical activity in several individual neurons, as the rats ran in a T-shaped maze. According to the cue they were given, the rats were rewarded for correctly picking left or right as they approached the T.
The investigators centered on two neurons: projection neurons - which send messages from the striatum to the neocortex to start or stop movement; and fast-spiking interneurons - which allow local communication within the striatum.
Among the projection neurons, the researchers found two subtypes: those that were active minutes before the rats started running and those that were active during the run.
Surprisingly, the researchers found that in the dopamine-absent striatum - the projection neurons developed generally normal activity patterns.
Before or during the run, they became even more active - these hyper-drive effects were associated with whether the rats learned the maze task or not.
The interneurons on the other hand, never developed the patterns of firing seen in normal interneurons while learning - even after the rats learned to run the maze. The local circuits were deactivated.
Reestablishing Neuron FunctionWhen treated with L-dopa, the rates had normal activity restored in the projection neurons - but it did not restore normal activity in the interneurons.
A reason for this could be that cells become disassociated by the loss of dopamine, despite L-dopa being given - the local circuits cannot be altered to respond to it.
The current study is the first of its kind to reveal that the effects of dopamine loss depend on the type of neuron as well as the phase of task behavior - and how well the task has been learned.
The research team will now work on calculating dopamine levels in different parts of the brain as the dopamine-drained rats learn new behaviors.
Written by Kelly Fitzgerald
Copyright: MediLexicon International Ltd
Original article posted on Medical News Today.
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