Natalie Hunter investigates a cutting-edge technique that is helping researchers better understand how the brain works
Imagine being able to switch off the neurons that control an individual’s fear response, turning a normally shy, timid creature into one unafraid of the unknown. Sound far-fetched? Well, researchers have achieved this with mice using a technique known as optogenetics.
How does optogenetics work?
Optogenetics involves genetically modifying cells in order to make them sensitive to optical stimuli, meaning that their activity can be controlled by light. Years ago, researchers discovered proteins in some types of algae that respond to a specific wavelength of light; often these proteins are cell membrane ion channels, and so open or close in response to light.
Scientists hypothesised that if they inserted these proteins into the cell membranes of neurons, they might be able to control brain processes, using light to open and close ion channels to produce or inhibit action potentials. This, they thought, would be revolutionary, because it would make it possible to switch on and off specific groups of neurons at specific times, allowing scientists to test their role in behaviour with much greater precision. Prior methods of electrical brain stimulation had not been able to distinguish between particular groups of neurons, and also hadn’t been able to avoid stimulating nearby axons of cells in other neural networks. The specificity allowed by optogenetics would overcome these issues.
Optogenetics is often achieved using the well-established technique of transfection. The gene in the algae which codes for the specific light-responsive protein, known as an opsin protein, is isolated. It is then inserted into a virus, which acts as a vector (though it is modified so that it can’t cause disease), entering a host cell and forcing it to express the genetic material it is carrying. A ‘promoter’ DNA region that only allows expression in specific cells is also included in the transfected genetic code, to make sure the opsin protein is only produced in the desired cells.
What can optogenetics be used for?
Most optogenetic experiments so far have been done on model animals such as mice, and some exciting results have been produced. A lot of research has been done in the mouse amygdala, the brain region responsible for some emotions, including fear.
Mice are normally timid. Hesitant to enter large open spaces, they will sniff and investigate their environment before moving around. In one experiment, researchers transfected opsin genes into neurons in a mouse’s amygdala, and then implanted a light-emitting diode (LED) into the skull in such a way that the targeted neurons were able to detect it. When the LED was switched on, the targeted neural circuit in the amygdala was inactivated, and the timid mouse suddenly became brave, venturing into open space without hesitation. When the light was switched off, the mouse scurried back to a corner.
Experiments like this can give unprecedented insight into the workings of the brain. They are letting scientists directly identify how specific neurons and circuits regulate specific behaviours for the first time.
Can we start using optogenetics to treat human diseases?
Some researchers argue these experiments show how optogenetics could be used to treat certain human diseases. For example, the experiments on fear in mice could potentially translate into treatments for anxiety disorders in humans. Work is being done to see if optogenetics could be used to treat neural illnesses such as Parkinson’s disease, in a similar way to transcranial magnetic stimulation (read our article on TMS here).
However, there are many barriers to be overcome. First of all, the process of injecting a virus into a person’s brain cells may carry risks, and public acceptance of such a procedure may be difficult to obtain. Secondly, it is very invasive; studies in mice require an LED to be inserted into the skull or spinal cord. Thirdly, our understanding of the many neural networks that underlie complex disorders and behaviours is still very limited, so we are not yet in a position to begin controlling them in humans.
But further optogenetic studies on model animals will increase our understanding of how the brain works, and in a way that traditional stimulation methods cannot. While the therapeutic use of optogenetics may be a long way off, its value as a research method is undeniable.Lead image:
Juan Pablo Colasso/Flickr CC BY NC ND
- Making sense of optogenetics (2015)
- BitesizeBio: Principles and mechanisms of mammalian cell transfection
- MIT Technology Review: An on–off switch for anxiety
- Scientific American: Revolutionary neuroscience technique slated for human clinical trials
Questions for discussion
- Once opsin genes have been transfected into an individual’s cells, this is irreversible. What would this mean if optogenetics were to be trialled in humans?