Francis Crick the co-discover of DNA had an idea back in 1999, an idea that at the time seemed highly far fetched to many; the possibility of genetically engineering a neuron so that it could be switched on and off by exposure to light.

 

This idea was never fully formulated by Crick, but others within the scientific community got to work and not long after this initial speculation, Stanford Professor Karl Deisseroth and his colleagues managed to use a virus to introduce light sensitive genes from algae directly into rat neurons.

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Through exposure to a type of blue light the researchers could now cause neurons to fire at will, and soon after were able to introduce another gene through bacteria, that suppressed neurons when exposed to green light. Thus a type of on / off switch using nothing more than light was born. This technique now widely used, is known as ‘optogenetics’.

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Since the development of optogenetics it has been widely adopted, and hundreds of labs around the world are implementing similar techniques to probe areas of the brain with increasingly finer control. But why does this matter? Well, by being able to turn on cells and sub-sets of cells, we are able to observe what sorts of behaviours they initiate.

 

Similarly by being able to turn off cells momentarily, we can study the types of behaviours they are necessary for; allowing us to observe how smaller networks contribute to larger networks, more widespread brain activity, and the subsequent behaviours and diseases states that can arise from particular neural configurations.

 

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“Optogenetics has revolutionised neuroscience, It has allowed neuroscientists to manipulate neural activity in a rigorous and sophisticated way and in a manner that was unimaginable 15-20 years ago.”  

Rob Malenka, Professor of Psychiatry and Behavioural Sciences. 

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Other applications of this technique might come in the development of new pharmaceutical interventions. Drugs often target molecules which can be present in a variety of different areas in the brain, and although many are effective, the potential for finer control over subsets of cells through optogenetics could allow for the development of more highly specified and effective drugs for a variety of different purposes. 

 

Below are a few examples of some of the questions researchers have been exploring with the use of optogenetics and some key discoveries:​

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 1. Reactivating memories with light 

 

Engram cells retain memory under retrograde amnesia. 

Ryan TJ, Roy DS, Pignatelli M, Arons A, Tonegawa S.

Science (2015) doi: 10.1126/science.aaa5542

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Ryan and colleagues, a group from MIT, discovered that memories that appear to be lost can be recalled by directly stimulating the specific neurons associated with a memory with light.

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 2. Sight restored in blind mice with novel Opto-mGluR6 receptor 

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​Restoring the ON switch in blind retinas: opto-mGluR6, a next-generation, cell-tailored optogenetic tool.

Van Wyk M, Pielecka-Fortuna J, Löwel S, Kleinlogel S.

PLOS Biology (2015)  doi: 10.1371/journal.pbio.1002143

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A promising new treatment for hereditary blindness has used optogenetics to introduce light-sensitive proteins into surviving retinal cells, turning them into replacements for the affected photoreceptors.

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This promising study has led to the approval of clinical trials, and the development of the first gene therapy drug based on optogenetic techniques. This drug aims to restore light sensitivity to the retinas of patients suffering from a genetic condition that leads to the degeneration of rod and cone receptors.

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 3. CRISPR gene editing enhanced thanks to optogenetics 

 

​Photoactivatable CRISPR-Cas9 for optogenetic genome editing.

Nihongako Y, Kawano F, Nakajima T, Sato M 

Nature Biotechnology (2015) doi: 10.1038/nbt.3245

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Since the discovery of the technique, scientists have enhanced the potential for CRISPR gene editing by developing optogenetic photoswitches, based upon Cas9 nuclease and ‘Magnet’ proteins, which allows for finer control of the CRISPR gene editing system.

 

Professor Moritoshi Sato, and his colleagues from the University of Tokyo, managed to engineer a photo-activatable Cas9 (paCas9), which will enable greater precision of the gene editing technique.

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