Release Subtitle: New mutant light-sensitive ion channels may become an effective and highly functional tool in fundamental neuroscience research
Release Summary Text:
In neuroscience, tools for controlling the activation and deactivation
of individual nerve cells are crucial to gain insights into their
functions and characteristics. Now, scientists from Okayama University,
Japan, have produced mutant variants of a membrane protein that can
effectively silence neurons when illuminated. The silencing effect can
be quickly “toggled” on and off using green and red light sequentially,
providing a more sophisticated tool than those currently available.
Full text of release:
In many human endeavors, having good tools for a particular task is an
essential requirement to obtain the best results possible, and
neuroscience is no different than other scientific fields in this
regard. However, neuroscientists tackle the colossal objective of
shedding light on the inner workings of neurons and neuronal circuits,
and they rely on various methods to observe and control the firing of
neurons to gain a better understanding of their functions.
Optogenetics has been regarded as one of the most impactful
breakthroughs in neuroscience over the last decades. It involves using
light of specific frequencies to control neurons in genetically modified
organisms. Neurons, like all cells, have “ion channels”—membrane
proteins that can be opened or closed and regulate the flow of charged
particles in and out of the cell, thus regulating the electrical
behavior of neurons. Now, thanks to optogenetics, they can be altered to
be light-sensitive—light essentially can be used to open or close these
channels in genetically modified organisms, giving researchers control
over which and when neurons fire. Now, a new study by scientists from
Okayama, Japan, proposes a promising new tool based on optogenetics for
studying neurons. But why is this tool so attractive to neuroscientists?
Read on to know more.
While optogenetics has certainly facilitated our understanding of
neurons, the technique has some limitations. In particular, the
available light-sensitive variants of negatively charged ion, or
“anion,” channel proteins, which regulate the flow of negatively charged
ions, are much less diverse than their positively charged ion, or
“cation” channel counterparts (for positively charged ions). Whereas
light-sensitive cation channels can be used to “activate” neurons using
light, light-sensitive anion channels act as neuron “silencers” that
prevent the neuron from firing when illuminated at the right frequency.
This new study by Japanese scientists, published in The Journal of
Physical Chemistry Letters, expands the available options for
optogenetic neuronal silencing, and explores the potential of GtACR2, a
natural light-regulated anion channel from an alga.
The scientists first introduced strategic mutations in GtACR2 amino
acids to produce more light-responsive anion channels and tested the
results using Escherichia coli bacteria. They found a shift in the
frequency that was required to open the channel. The mutant GtACR2
channels also remained open much longer than their normal counterparts.
Dr Yuki Sudo, Dr Keiichi Kojima and Ms Natsuki Miyoshi of Okayama
University, who led the study, remarks: “Long-time neural inhibition
generally requires repetitive long-lasting illumination; however, this
invariably heats tissues, causing physiological and behavioral changes
and tissue damage. Using the observed prolonged channel opening, GtACR2
mutants would be an effective neural silencer over long-term scales with
lower illumination time and fewer heat-dependent effects.”
GtACR2 mutants can also be activated and inactivated by illuminating
them with different light frequencies. Irradiating the channels with
green light opens them, silencing the neuron, but irradiation with red
light causes them to quickly close. This “step-functional” property
could give future scientists finer control over the state of the
channels and the associated neurons, providing a more sophisticated tool
for neurological experiments.
Having a highly controllable, long-lasting neural silencing technique is
invaluable in all fields of neuroscience, both from basic research and
applied science viewpoints. In this regard, Dr Kojima adds: “In humans,
neural inhibition plays essential roles in many physiological phenomena,
such as sleep, awaking, circadian rhythms and hormone secretion. We
expect that our understanding of the above phenomena at the molecular
level will be accelerated by optogenetic neural silencing using our
engineered proteins, and that this will lead to development of new
treatments for sleep disorder, jet lag and lifestyle-related diseases.”
The tool unveiled in this study will hopefully lead to many advances in
medicine and neuroscience, as scientists continue the quest to answer
one of the hardest questions ever known: how exactly do neurons and the
brain work?
Release URL: https://www.eurekalert.org/pub_releases/2020-08/ou-abi081820.php
Reference:
Title of original paper: Green-Sensitive, Long-Lived, Step-Functional
Anion Channelrhodopsin‑2 Variant as a High-Potential Neural Silencing
Tool
Journal: The Journal of Physical Chemistry Letters
DOI: http://dx.doi.org/10.1021/acs.jpclett.0c01406
Contact Person: Yuki Sudo, Keiichi Kojima
sudo(a)okayama-u.ac.jp, keiichikojima(a)okayama-u.ac.jp
For inquiries, please contact us by replacing (a) with the @ mark.
https://www.okayama-u.ac.jp/eng/research_highlights/index_id110.html
https://sdgs.okayama-u.ac.jp/en/
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