New optogenetic tool for understanding epileptic seizures

10 August 2021


The discovery of natural and engineered light-sensitive proteins has developed a versatile and easy-to-use method in neuroscience called optogenetics that uses a light stimulus to precisely regulate neural activity in time and space, and has had an immense impact on understanding neural networks, neuronal function, and signaling pathways.

Scientists at the Ruhr-University Bochum, Germany, have now discovered a new optogenetic tool and demonstrated its potential in epilepsy research. This tool, a member of a family of proteins called opsins found in the brain and eyes in zebrafish, continuously activates an important intracellular signaling pathway called the Gi/o pathway.

Unlike other optogenetic proteins that are turned on when light is shone on them, this protein (Opn7b) is turned off by blue or green light. Characterization of Opn7b that the scientists reported in an article in Nature Communications, “Reverse optogenetics of G protein signaling by zebrafish non-visual opsin Opn7b for synchronization of neuronal networks,” will allow researchers to interrupt the continuously active Gi/o signaling pathway transiently, by shining blue or green light on Opn7b.

The teams, led by Melanie Mark, PhD, scientist at the behavioral neurobiology research group and Stefan Herlitze, PhD, professor and scientist at the department of general zoology and neurobiology, showed that shining light on Opn7b deactivates the permanently active Gi/o pathway that normally opens specific ion channels resulting in an influx of ions into the cell and downstream steps in the signaling process. Raziye Karapinar, PhD, Ida Siveke, PhD, and Dennis Eickelbeck, PhD, characterized the function of Opn7b in detail and identified that the receptor protein is deactivated by light.

“This suggests that light acts as an inverse agonist for Opn7b and can be used as an optogenetic tool to inhibit neuronal networks in the dark and interrupt constitutive inhibition in the light,” the authors noted.

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