Emerging Technologies Optogenetics

A new method has been developed that enables scientists to control specific events in targeted cells of living tissue. This emerging technology is known as optogenetics.

The technology, chosen by the interdisciplinary research journal Nature Methods as the Method of the Year (MOTY) across all scientific and bioengineering fields in 2010, has become a very useful tool in the field of medical science. Optogenetics was also featured in the article “Breakthroughs of the Decade” in Science, a scientific research journal.

What is optogenetics?

Optogentics combines genetic and optical methods to precisely analyze biological activity at the cellular level. This technology was developed in 2005 by a group led by Karl Deisseroth, MD, PhD, associate professor of bioengineering and of psychiatry and behavioral science at the Stanford University School of Medicine.

Optogenetics is a complex technology which is essentially made up of targetable control tools that are sensitive to light and deliver effector function; as well as enabling techniques. These enabling technologies comprise tools used in delivering light into tissues being studied; techniques used for targeting the control tools to cells under investigation and tools used to obtain and analyze readouts, such as targeted imaging or electrical recording of the triggered biological activity.

Francis Crick suggested in 1979 that the main challenge faced by neuroscience was the need to control specific brain cells without affecting other cells. Electrodes are not suitable for precise targeting of defined cells and drugs are too slow in evoking effect. Thus, Crick hypothesized that light might be able to serve as a control tool, but neuroscientists did not know then of any definite technique to render specific cells sensitive to light.

But four decades ago microbiologists were aware that some microorganisms produce light-gated proteins that act as direct regulators of ion transport across the plasma membrane. Stoeckenius and Oesterhelt found out in 1971 that bacteriorhodopsin works like an ion pump that readily responds to visible-light photons. And over the years, the idea of a single-gene, single-component control went on with the discovery of other light-activated proteins, such as the halorhodopsin in 1977 and channelrhodopsin in 2002.

But what scientists considered then were multi-component strategies that did not involve any microbial opsin genes but rather surges of various genes or combinations of synthetic chemicals and genes. It was not until 2005 that these two fields were brought together because it was believed that such a strategy was not likely to work.

Deisseroth and his team used a single-gene single-component technique by inserting a gene for a photosensitive algal protein into mice brains, where it penetrated the nerve cells. When the modified nerve cells are exposed to light, by way of the fiber-optic implant, the protein stimulates electrical activity within the cell.

Millisecond precision is a key feature of optogenetics. It enables the researcher to keep pace with rapid biological information processing within nerve cells. This is important because by definition, optogenetics must work on the millisecond timescale to make way for addition and deletion of precise activity patterns with specific neurons in the brains of intact animals. And it is equally vital to have fast readouts in this technology that can keep pace with optical control. This is accomplished by electrical recordings using optrodes or by the use of biosensors (fluorescent proteins fused to detector proteins).

Characteristically, optogenetics introduces fast photosensitive channels and enzymes that allow researchers to temporarily manipulate electrical and biochemical events with millisecond precision without sacrificing cell-type resolution by using specific targeting mechanisms. Among the proteins which can be utilized to study the function of neural systems are microbial opsins called channel rhodopsins. These proteins are used to activate nerve cells. To inhibit neural function, including in freely-moving mammals, halorhodopsins, archaerhodopsin (Arch), Leptosphaeria maculans fungal opsins (Mac), as well as enhanced bacteriorhodopsin (eBR) have been used.

Using combined genetic and optical techniques, optogenetics involves the development of genetic targeting strategies and integrated fiber-optic and solid-state light sources to enable scientists to control specific cell types, even those lying deep within the brain, in freely behaving animals.

Moreover, optogenetics is a promising tool in studying the function of other vital organs and systems like the heart, pancreas and the immune system. In his commentary, Deisseroth mentions that “optogenetics addresses a much broader unmet need in the study of biological systems: the need to control defined events in defined cell types at defined times in intact systems.”