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Introduction to Optogenetics

Common optogenetic tools for inducing depolarizing and hyperpolarizing events [1]
Common optogenetic tools for inducing depolarizing and hyperpolarizing events [1]




Year Event
1971 Bacteriorhodopsin (yellow and green) found in Halobacterium halobium
1977 Halorhodopsin (yellow) found in Halobacterium halobium
1999 Francis Crick's Declaration
2002 ChR1 (blue) discovered in Chlamydomonas reinhardtii, Zemelman and Miesenbock chARGed optogenetic system [2]
2003 ChR2 (blue) discovered in Chlamydomonas reinhardtii
2005 Millisecond-timescale, genetically targeted optical control of neural activity [3]
2006 "Optogenetics" coined
2008 VChR1 found in Volvox carteri (yellow and possibly green)

The story behind optogenetics is a story of convergence of two seemingly unrelated fields: microbial microbiology and neuroscience. In 1971, Walther Stoeckenius and Dieter Oesterhelt discovered Halobacterium halobium contained transmembrane protein bacteriorhodopsin (BR) that is capable of moving ions in the presence of light. BR is highly expressed in haloarcheal membranes while a similar transmembrane protein proteorhodopsin (PR) is expressed in eubacteria.

In 1977, Matsuno-Yagi and Mukohata described the ion pump channel halorhodopsin which displaces extracellular chloride ions in to the cell. As these discoveries were happening in the background, a growing desire to effectively control the neurons was ever prevalent. During this period, neuroscientists adopted the idea that cognitive processes were distributed in various localizations of the cortex. This fact was evident when lesions in specific areas of the brain would lead to loss of a specific process.


This lack of cell specificity and cellular controls encouraged neuroscientists to find alternative methods. In the 1990s, some scientists became infatuated with the idea that opsins may be the key to cell specificity. However, for the most part, this idea was considered too “far-fetched” to allocate resources, time, and money.

In 1999 at the University of California in San Diego, Francis Crick commented that neuroscience faced a major challenge: controlling one type of cell while leaving the others unaffected. Crick even suggested that light could serve as a control tool. In 2002, Boris Zemelman, currently a UT associate professor, and Gero Miesenbock conducted the earliest genetically targeted method with rhodopsin photoreceptors in Drosophila.




Biochemistry behind Optogenetics


BR process:

  2. confirmation shift and dipole of RSHB+ raises pK, releasing RSB proton (deprotonated retinal Schiff base) and created M intermediate (410nm maximum absorbance)
  3. Release RSB proton is accepted by the Asp 85
  4. Simultaneously, a different proton is released from an amino acid group from the proton release complex (PRC)
  7. Asp 85 transfers its proton to the PRC




The Optogenetic Process

  5. Record transformed regions

Gene Delivery


Controlled Illumination




Applications of Optogenetics





Recently, by using optogentic tools, scientist have restored vision to blinded mice, by splicing ChR2 protein into the retina of the mice. Through rAAV, the opsin genes were transformed into ON bipolar cells. [8]

IGEM Take-home Message


Other Light Sensors

Light responsive proteins or "light sensors" are currently used as an method of signal transduction in order to regulate genetic circuits non-invasively within organisms. Light sensor proteins are found in all domains of life and have been utilized in complex genetic regulation to willfully turn off or on a gene of interest. Incidentally, the light sensor protein is a transmembrane channel or receptor found directly on the surface of most organisms. Particularly, the the majority of these light sensors consist of photoreceptors. In brief, a photon hits the photoreceptor and initiates a conformational change leading to possible phosphorylation by kinase or delocalization of trascription factor. Subsequently, this creates a biochemical signalling cascade that induces a molecular mediatory molecule to interact with the following regulatory molecules or simply interact with the gene complex. Photoreceptors are multidomain effector proteins that contain the protein component, pigment, and the chromophore. The the pigment acts as a antennae station to attract photons. Photon acquirement lead to a change in the aromatic structure of chromophore which initiates the comforational change. By creating chimeras and other fusion proteins, an individual can easily take advantage of an promoter/ regulatory molecule to build new cascades thereby affecting different genetic ciruits.[9]

Types of Photoreceptors

  1. rhodopsins- retinal chromophore, visual light used in eye cells.
  2. phytochromes- bilin chromophore, red light detection used by plants for circadian rhythm.
  3. xanthopsins- trans-p-coumaric acid chromophor, blue light avoidance response used by Ec. halophila
  4. cryptochromes- cryptochrome chromophore, blue-green light used by animals for circadian clock to seed germination in plants
  5. phototropins- Flavin chromophore (FMN), blue light for signal transduction in algae and bacteria
  6. BLUF- Flavin chromophore (FAD), blue light signal transduction in proteo- and cyano-bacteria [10]


  1. Optogenetics: controlling cell function with light [Pastrana2010]
  10. van der Horst MA and Hellingwerf KJ. . pmid:14730990. PubMed HubMed [VanderHorst2004]
All Medline abstracts: PubMed HubMed
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