Optogenetics Study Upends Decades Of Parkinson’s Research

Contrary to earlier assumptions, Parkinson’s disease symptoms are caused by hyperactivity rather than suppressed activation of a brain region known as the thalamus.

AsianScientist (Oct. 2, 2017) – Scientists in Korea and Singapore have demonstrated that hyperactivity in the thalamus of the brain causes the tremors, rigidity and loss of voluntary movement in Parkinson’s disease patients. Their findings are published in Neuron.

It is known that Parkinson’s disease is caused by a lack of dopamine, a chemical in the brain that transmits neural signals. However, it remains unclear how the motor problems associated with Parkinson’s disease arise.

Smooth, voluntary movements, such as reaching for a cup of coffee, are controlled by the basal ganglia, which issue instructions via neurons in the thalamus to the cortex. These instructions come in two types: one that triggers a response (excitatory signals) and the other that suppresses a response (inhibitory signals). Proper balance between the two types of signals controls movement.

A low level of dopamine causes the basal ganglia to severely inhibit target neurons in the thalamus. Scientists have long assumed that this stronger inhibition causes the motor problems of Parkinson’s disease patients.

In this study, the research team used optogenetic technology in an animal model to study the effects of this increased inhibition of the thalamus which ultimately affects movement.

“Our findings are a breakthrough, both for the understanding how the brain normally controls the movement of our body and how this control goes awry during Parkinson’s disease and related dopamine-deficiency disorders,” said Professor George Augustine of Nanyang Technological Univesity, Singapore.

The researchers found that when signals from the basal ganglia are more strongly activated by light, the target neurons in the thalamus paradoxically became hyperactive. Called rebound excitation, this hyperactivity produced abnormal muscular stiffness and tremors. Such motor problems are very similar to the symptoms of Parkinson’s disease patients.

When this hyperactivity of thalamic neurons was suppressed by light, mice moved normally without displaying Parkinson’s disease symptoms. This proved that the hyperactivity is the cause of motor problems experienced by Parkinson’s disease patients.

“This study overturns three decades of consensus on the provenance of Parkinsonian symptoms,” said Professor Kim Daesoo at the Korea Advanced Institute of Science and Technology.

“The therapeutic implications of this study for the treatment of Parkinsonian symptoms are profound. It may soon become possible to remedy movement disorders without using L-DOPA, a pre-cursor to dopamine,” added study lead author Dr. Kim Jeongjin.

The research team will intends to further investigate how hyperactive neurons in the thalamus lead to abnormal movement. They also hope to develop therapeutic strategies for the disease by targeting this neural mechanism.


The article can be found at: Kim et al. (2017) Inhibitory Basal Ganglia Inputs Induce Excitatory Motor Signals in the Thalamus.

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Source: Korea Advanced Institute of Science and Technology; Photo: Shutterstock.
Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.

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