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New Optogenetic Silencing Tool Can Manipulate Complex Biological Processes

[Estimated read time: 3 minutes]
  • New optogenetic tool uses laser to ‘switch off’ the electrically excitable cells. 
  • It reduces harmful side effects through artificial ion fluxes that were inevitable with the existing optogenetic inhibitory tools.

Optogenetics is a technique that uses light to alter the molecular event in a particular manner in living tissues, mostly neurons that have been genetically modulated to express light-sensitive ion channels. To change the behavior of the cell, the method utilizes genetically-encoded proteins that alter configuration in the presence of light.

The behavior of a single cell, cellular network, and even whole organism can be controlled with high time and spatial resolution. The field of optogenetics has improved the fundamental scientific understanding and made it possible to analyze specific types of cells in an intact tissue. It has lead to insights into several neurological and psychiatric disorders, including Parkinson’s disease.

Now, researchers at the Humboldt University of Berlin, Germany, have come up with an advanced version of the optogenetic tool that enables the examination of missing electrical signals which take place after a heart infarct. It could pave the way for the development of new treatments and plan new applications for examination of neuronal networks.

Many kinds of research have been dedicated to building systems for optogenetic inhibition of excitable cells. Such systems provide a detailed view of what a specific type of cell does in the complex functional architecture of excitable tissue like brain and heart. For their efficient utilization, optogenetic inhibitors should be

  • Targetable to particular cells.
  • Allow reversible action potential firing for variable durations.
  • Should not have negative effects on ion concentrations that could impact associated organ functions.

Light-gated channels are proteins that get triggered or ‘switched-on’ by the laser activity of electrically excitable cells. It regulates the electrical activity in complex cellular networks, and thus the behavior of cells.

Optogenetic tools to ‘switch of’ these electrical activities is equally important. The existing established proteins can do the same but have harmful side effects.

Reference: Nature Communications | doi:10.1038/s41467-018-07038-8 | Humboldt University of Berlin

‘Switching-Off’ Excitable Cells

The new two-module optogenetic tool relies on the concurrent expression of a photoactivated enzyme (PAC) and a bacterial potassium channel (K). Together, PAC and K make it possible to suppress neurons activity for a few seconds by using a short blue light pulse. Researchers did mention that the PACK activation can effectively arrest movements in zebrafish.

Besides its ‘silencing’ feature, the tool is also known to have a high light sensitivity, especially to blue and ultraviolet light. Combined with the ability to integrate light over time, this new tool can minimize activation of any co-expressed channelrhodopsin (a subfamily of protein that functions as light-gated ion channels).

Read: The First Brain-to-Brain Interface Lets 3 People Share Thoughts Directly To Each Other’s Head

The tool reduces unpleasant side effects through artificial ion fluxes that were inevitable with the existing optogenetic inhibitory tools. Moreover, it’s useful in several model systems and across disciplines exploring excitable cell systems, from cardiovascular to neuroscience researches.

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