Optogenetics enables scientists to study neural circuits and ion channels. Findings can enable scientists to create custom-made specific proteins that are optimized for optogenetic experiments.

Using the revolutionary technology of optogenetic techniques, scientists have been able to study and understand the functioning of neural circuits and light-sensitive proteins such as channelrhodospins. Researchers from UC Santa Cruz have now determined various molecular mechanisms associated with the light-induced activation of one such protein.

The findings, published in two papers in the Journal of Biochemistry, can enable scientists to create custom-made specific proteins that are optimized for optogenetic experiments.

Research Study

Senior author of both the papers and Professor of Chemistry and Biochemistry at UC Santa Cruz, David Kliger, explained that scientists previously had very little knowledge about the functional mechanisms of light-sensitive proteins, despite their wide use in optogenetics.

For studying the basic function of channelrhodospin-2 – found in a specific type of marine algae and commonly used in optogenetics – the research team used fast laser spectroscopy. Channelrhodospins are basically light-gated ion channels that regulate the movement of ions across cell membranes, and there are many different kinds serving different functions.

It is known that nerve signals are generated when ions flow across the membrane of a nerve cell, and scientists made a breakthrough in optogenetics when they discovered that inserting genes for light-gated ion channels into nerve cells could activate them into firing signals when exposed to light.

Findings And Significance

The first paper highlights the mechanisms behind the function of channelrhodospin, with respect to the intermediate states the protein goes through to open the ion channel. The second paper demonstrates that these mechanisms can help explain the patterns of ion currents observed during optogenetic experiments.

“The findings are exciting because they open up a methodology to start selecting mutant proteins with properties optimized for optogenetics”, Kliger commented. “This can be extremely important for brain research and for studying neurological processes in general”.

Kliger explained that various types of modifications could facilitate optogenetic experiments, such as increasing the efficiency of proteins so they respond to lesser amounts of light during neural activation. Speeding up or slowing down the opening or closing of the channel may also be possible. Depending on the location of the channel, researchers could also change the type of light (spectrum and wavelength) to which the protein channels normally respond.

“These basic biophysics experiments can help in optimizing how the proteins function in optogenetics experiments”, Kliger concluded.