Optogenetics

Imagine being able to control brains using lasers. Sounds like science fiction, right?

Enter optogenetics – a cutting-edge neuroscience research tool which allows researchers to literally turn brain cells on and off using light.

The huge advantage of optogenetics is that it gives unparalleled control over groups of selectively targeted cells within a brain circuit. Using this, we can start to unravel in more and more detail how brains are working and what goes wrong in neurological diseases.

How does it work?

The good news for all you conspiracy theorists out there is that optogenetics relies on the presence of light-sensitive proteins, which are not present in normal mammalian brains. In fact channelrhodopsin – one of the most common optogenetic activators – actually comes from green algae, where it helps them to move in response to light.

So how do optogenetic proteins get into a mammalian brain? This is where the ‘genetic’ aspect of optogenetics comes in – we can use gene therapy to insert the protein into the brain. You can check out the primer on gene therapy for more details but in short it goes something like this:  1. We take a virus that has been modified so that it can’t cause disease. 2. We put DNA for our optogenetic protein inside the virus. 3. We inject the virus into the brain. 4. The virus naturally invades brain cells but, instead of causing disease, it inserts the genetic code for optogenetic protein into the cells. 5. Brain cells make optogenetic protein.

What can we do with optogenetics?

With our optogenetic protein safely expressed in the brain, we can start to manipulate brain activity by shining light. At an experimental level this is incredibly powerful. First – controlling cells using light damages the tissue much less than using electrodes, for example. Second, we have the ability to simultaneously control only those cells where we decided to express the optogenetic protein. This is not possible using other approaches like electrophysiology (primer to come soon!) and it lets us see the impact of manipulating specific brain circuits, giving us vital clues about how they work.

Can it be used to stop epilepsy?

Since optogenetics gives us the ability to control brain activity, it makes sense that it could be used to stop seizures. The idea would be to have some kind of detector which can switch on a light inside the brain when a seizure is starting. The light would stop the seizure and then the detector would switch off again. Indeed, there is experimental evidence that seizures can be effectively stopped using this technique.

Still, considerable barriers remain before optogenetics could be used clinically. Perhaps the biggest challenge is how to deliver light to the brain. In experimental settings, light has to be delivered to the brain using an optical fibre placed on the surface of the brain, which would be incredibly invasive for patients. Moreover, it is difficult to target structures which are deep inside the brain as the light simply does not reach that far. The heat generated by the optical fibre also has the potential to be damaging to the brain. Finally, the therapeutic application of optogenetics is probably limited to focal epilepsies – those where seizures always start in the same place. In epilepsies where seizures do not always have the same physical starting point it would be impossible to target the therapy to the correct part of the brain.

In short, optogenetics is a highly powerful research tool which can be used to better understand how brains work in health and in disease. It does have therapeutic potential but, at the moment, there are huge challenges which have to be overcome before it can be used.

Highlights

  • Optogenetics lets us switch genetically targeted brain cells on or off using light
  • It gives unparalleled control of entire brain circuits and so it is a very powerful research tool
  • There is experimental evidence that optogenetic strategies can stop seizures in epilepsy
  • There are still big clinical challenges before optogenetics could be used in patients