Wednesday, February 1, 2023

A new tool for examining processes in the cerebellum

The Bochum research team: Bianca Preissing, Lennard Rohr, Ida Siveke and Tatjana Surdin (from left)
Photo Credit: © RUB, Marquard

Light can start a signal cascade in the cerebellum. This also illuminates processes that play an important role in cerebellar diseases.

Processes in the cerebellum are involved in various diseases that affect motor learning. A new tool developed by a Bochum working group helps to investigate this better: a light-activated protein that is coupled with part of an exciting receptor. Thanks to this optogenetic tool, light can activate a signaling pathway in the nerve cells of the cerebellum and observe its effects. So, the group around Dr. Ida Siveke from the working group of Prof. Dr. Stefan Herlitze at the Ruhr University Bochum show that the signal path is involved in cerebellar-controlled motor learning. The researchers report in the iSience journal.

The brain adapts

One of the most fascinating properties of the human brain is its ability to be plastic. This means that the brain adapts its activity to external and internal conditions. This can change the function of neural circuits as well as behavior, thoughts or feelings. Neural plasticity can be caused, for example, by changes in the hormonal balance due to development or disease, but also by medication or genetic changes. In order to investigate the influence of individual groups of nerve cells or receptors on them, researchers use optogenetic methods. Light-activated proteins are used to visualize neural signals or to control cell functions through light.

The so-called metabotropic glutamate receptor of type 1 - mGluR1 for short - plays an important role in the neuronal plasticity of the cerebellum. Its activation means that certain interfaces between nerve cells, the so-called synapses, change.

A tool helps to look into the cerebellum

"In order to investigate and modulate the plasticity in the cerebellum, we have developed an optogenetic tool with which we can control the mGluR1 signal cascade through light," report Ida Siveke and Tatjana Surdin. This tool called OPN4-mGluR1 consists of a light-sensitive protein, melanopsin or OPN4, which is coupled to part of the mGluR1 receptor and can be introduced into different cells and produced there. “This enabled us to activate the signal path in the same way that it happens naturally. But now through light,” explains Tatjana Surdin. The consequences of activation are an increase in the calcium concentration in the nerve cells and an increase in activity in certain cells of the cerebellum, the so-called Purkinje cells. By activating the signal path, the function of a specific synapse, the parallel fiber Purkinjezell synapse, was reduced for a long time. Motor learning controlled by the cerebellum could also be improved by light activation. "This means that our OPN4-mGluR1 tool opens up new possibilities for examining various types of cerebellar-associated diseases, such as spinocerebellar ataxias, which are based on the dysfunction of mGluR1 signal transmission and neuronal plasticity," said Ida Siveke.

Funding: The work was funded by the German Research Foundation within the framework of the Collaborative Research Centers SFB 874 and SFB 1280 and as part of the priority program SPP1926.

Published in journaliScience

Source/CreditRuhr University Bochum

Reference Number: ns020123_01

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