A recent study has reported a scientific breakthrough that may inform new theories about Parkinson’s disease and lead to new, more effective treatments for the condition. The study was published after the completion of a five-year project conducted by scientists on the KAIST research team in Korea, in collaboration with scientists from the Nanyang Technological University in Singapore.
Researchers working to understand motor signals in the brain
The research group that published the study is focused on learning more about how the brain produces motor signals that underlie behaviors. The basal ganglia are a large group of neuron clusters in the brain, which controls complex motor behaviors through two types of signals transmitted via neurons in the thalamus. Inhibitory signals are those that suppress a motor response, while excitatory signals are those that trigger a motor response. The basal ganglia mainly produce inhibitory signals.
Researchers are still working to understand exactly how inhibitory and excitatory signals work together to regulate complex motor behaviors and control movement. Motor disorders such as Parkinson’s disease are caused by abnormal regulation of signals within the basal ganglia and thalamus. Researchers know that Parkinson’s disease is caused by a lack of the dopamine in the brain, which is a neurotransmitter chemical that helps transmit inhibitory and excitatory signals between neurons. However, it is still not known exactly how this lack of dopamine causes the motor symptoms of Parkinson’s disease, such as tremors, rigidity, and problems with voluntary movement.
Current theories about Parkinson’s disease suggest that the low level of dopamine in a patient’s brain strongly inhibits the target neurons in the thalamus by completely suppressing them (making them silent). However, the results of the new study show that inhibitory signals produced by the basal ganglia can actually produce excitatory signals in target neurons. This is a breakthrough scientific development about the role of the basal ganglia in motor behaviors. If the findings reported prove to be true in other studies, then the role of inhibitory signals produced by the basal ganglia in Parkinson’s disease patients will have to be reconsidered.
Target neurons were producing “rebound” firing
The study was carried out using an optogenic technology—which uses light to inhibit or activate neuron activity in the brain—in order to study how increasing the inhibitory signals produced by the thalamus affects motor behavior. In a series of studies using laboratory mice, the scientists used light to activate inhibitory signals in the basal ganglia, which resulted in the inhibition (suppression) of neuron activity in the thalamus. This was expected based on the current theories. However, at the end of the inhibition period, they found that many of the target neurons in the thalamus produced “rebound” firing, in which the neurons were producing strong, hyperactive excitatory signals rather than inhibitory signals. This rebound firing caused symptoms of muscle contractions, stiffness, and tremors in the mice, which are similar to symptoms of Parkinson’s disease.
To understand more about the role of rebound firing in patients with Parkinson’s disease, they carried out further testing on mice that had low levels of dopamine in their brains. They found that those dopamine-deficient mice did have higher levels of rebound firing in the target neurons in the thalamus. Next, they blocked the excessive rebound firing in those neurons using optogenetic light technology. When the amount of rebound firing was brought back down to normal levels, the mice no longer had the motor symptoms of muscle contractions, stiffness, and tremors.
The researchers believe that this evidence proves that motor symptoms of Parkinson’s disease are actually the result of abnormally high levels of rebound firing in the thalamus, which is caused by low levels of dopamine in the brain. This is a new breakthrough because current theories up until now had assumed that the inhibitory signals—not the excitatory signals—in target neurons of the thalamus were the cause of motor symptoms. The research team is now working on understanding more about exactly how the rebound firing causes the motor symptoms.
Breakthrough study may offer exciting possibilities for new therapies
The results of this study offer exciting possibilities for developing effective new treatments for the motor symptoms of Parkinson’s disease. For example, it opens up opportunities for developing treatments that could decrease the level of rebound firing in the thalamus, and for treatments that could better regulate the inhibitory signals produced by the basal ganglia that trigger the excessive rebound firing. Researchers are optimistic that this breakthrough may pave the way for effectively treating the motor symptoms of Parkinson’s disease without the need for treatment with levodopa.