Researchers at the Ruhr-Universität Bochum (RUB) have developed a new optogenetic tool, i.e. a protein that can be controlled in the living organism with light. They used an opsin - a protein found in the brain and eyes - from zebrafish and introduced it into the brains of mice. Unlike other optogenetic tools, this opsin is turned off, not on, by light. The experiments also revealed that the tool could be suitable for studying brain changes responsible for the development of epilepsy.
The teams led by Prof. Dr. Melanie Mark from the Behavioural Neurobiology group and Prof. Dr. Stefan Herlitze from the Department of General Zoology and Neurobiology describe the experiments and results in the journal Nature Communications.
Role in various diseases suspected
The opsin used, named Opn7b from zebrafish, is a so-called G-protein-coupled receptor. Unlike many other G protein-coupled receptors, it can be activated without a molecule binding to it, making it permanently active. Normally, activation of G protein-coupled receptors leads to the opening of certain ion channels and thus to ion influx into the cell as well as further signalling processes in the cell. In the case of Opn7b, light deactivates this permanently active signalling chain.
G protein-coupled receptors, which are activated without molecular binding, have so far been little studied, although it is suspected that they play a role in various neuropsychiatric diseases and in night blindness. They also appear to be involved in the development of virally triggered cancers.
Receptor characterised in more detail
Dr. Raziye Karapinar, Dr. Ida Siveke and Dr. Dennis Eickelbeck characterized the functioning of Opn7b in detail and found to their surprise that the receptor is deactivated by light. It thus behaves in exactly the opposite way to common optogenetic tools that can be switched on by light.
The researchers believe Opn7b is well-suited to provide further insights into how G protein-coupled receptors work, which can be activated without molecular binding - and to provide new insights into their role in the development of disease by studying the receptors in a time-controlled manner in specific cell types.
The Bochum researchers Dr. Jan Claudius Schwitalla and Johanna Pakusch modified certain cells in the cerebral cortex of mice in such a way that they produced Opn7b. When they deactivated the receptor with light, this triggered epileptic seizures in the animals - a result that the researchers had not expected. The seizures could be specifically switched on with light and interrupted with the help of further light-controlled proteins. The scientists hope that with the help of this optogenetic tool it will be possible to understand more precisely both the underlying mechanisms and the temporal processes in the development of epileptic seizures.