Reverse optogenetic tool developed

Date:
July 23, 2021
Source:
Ruhr-University Bochum
Summary:
A new optogenetic tool, a protein that can be controlled by light,
has been characterized by researchers. They used an opsin -- a
protein that occurs in the brain and eyes -- from zebrafish and
introduced it into the brain of mice. Unlike other optogenetic
tools, this opsin is not switched on but rather switched off by
light. Experiments also showed that the tool could be suitable
for investigating changes in the brain that are responsible for
the development of epilepsy.



FULL STORY ==========================================================================
A new optogenetic tool, a protein that can be controlled by light,
has been characterized by researchers at Ruhr-Universita"t Bochum
(RUB). They used an opsin -- a protein that occurs in the brain and eyes
-- from zebrafish and introduced it into the brain of mice. Unlike other optogenetic tools, this opsin is not switched on but rather switched
off by light. Experiments also showed that the tool could be suitable
for investigating changes in the brain that are responsible for the
development of epilepsy.


==========================================================================
The teams led by Professor Melanie Mark from the Behavioural Neurobiology Research Group and Professor Stefan Herlitze from the Department of
General Zoology and Neurobiology describe the experiments and results
in the journal Nature Communications, published online on 23 July 2021.

Role assumed in various conditions The opsin Opn7b is a G protein-coupled receptor which is found in zebrafish.

Unlike many other light-activated G protein-coupled receptors, it can
be activated without a light stimulus and is thus permanently active; researchers call this constitutively active. Normally, activation of G protein-coupled receptors leads to an opening of certain ion channels and
thus to the influx of ions into the cell as well as to further signalling processes in the cell. In the case of Opn7b, light deactivates this
permanently active signalling chain.

Little research has so far been conducted on G protein-coupled receptors
that are activated without stimulation, although it is presumed that
they play a role in various neuropsychiatric conditions and night
blindness. They also appear to be involved in the development of virally induced cancers.

Receptor characterized more precisely Dr. Raziye Karapinar, Dr. Ida Siveke
and Dr. Dennis Eickelbeck characterized the function of Opn7b in detail
and, to their surprise, identified that the receptor is deactivated
by light. In contrast, conventional optogenetic tools are switched on
by light.

The researchers consider Opn7b well-suited to gain further insights
into the function of G protein-coupled receptors that are constitutively
active -- and obtain new knowledge of their role in the development of
diseases in which the receptors can be examined in a time-controlled
manner in specific cell types.

Epileptic seizures The Bochum researchers Dr. Jan Claudius Schwitalla
and Johanna Pakusch changed certain cells in the cerebral cortex of
mice in such a way that they produced Opn7b. If they deactivated the
receptor with light, it triggered epileptiform activity in the animals,
which could be specifically controlled with light and interrupted with
the help of other light-controlled proteins. The researchers hope that
it will be possible to use this optogenetic tool to understand more
precisely both the underlying mechanisms and the timescales in the
development of epileptic seizures.

========================================================================== Story Source: Materials provided by Ruhr-University_Bochum. Original
written by Julia Weiler.

Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Raziye Karapinar, Jan Claudius Schwitalla, Dennis Eickelbeck,
Johanna
Pakusch, Brix Mu"cher, Michelle Gro"mmke, Tatjana Surdin, Thomas
Kno"pfel, Melanie D. Mark, Ida Siveke, Stefan Herlitze. Reverse
optogenetics of G protein signaling by zebrafish non-visual
opsin Opn7b for synchronization of neuronal networks. Nature
Communications, 2021; 12 (1) DOI: 10.1038/s41467-021-24718-0 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/07/210723105316.htm

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