Optogenetics: using light to control the brain
In 1979, Francis Crick, the father of genetics, said that the major challenge facing neuroscience is being able to control the firing of certain neurons in the brain, without altering the activity of others.
This was certainly true, because the other techniques employed by scientists at the time — and until as recently as 2005 — weren’t quite up to the task. The alternatives were pharmacological activation/inactivation using drugs, and electrical stimulation. Both of these techniques have poor spatial and temporal resolution, and neuroscience needed something more.
Today, we can shine a light on a part of the brain and activate it.
Neurons are electrically excitable cells. They contain channels that allow the flow of electrically charged particles (or ions) through them, thus generating a current. These channels are extremely important as they open/close at very specific times and permit the neuron to be activated. This is how neurons communicate with one another and make the brain what it is.
Neurons get activated because of light sensitive proteins found in algae
A bunch of smart people found a protein called channelrhodopsin (or ChR2) in algae (how cool is that?) which responds to light and guides its movement. They found a way to integrate the gene coding for the protein into the genome of a virus.
When that virus (harmless, of course) is injected into a part of the brain, the gene for ChR2 is transcribed and translated (the process for the conversion of a gene into a protein). Light sensitive cation channels (opsins) then get expressed in the desired brain region.
Another way in which we can do this is by creating transgenic mice that express the gene, without the need for a virus.
Now, we can command the brain with light.
With the use of lasers, computers and fibre optics, we can control thousands of neurons with millisecond timing. This level of precise control was impossible before.
Understanding and manipulating the brain
We already knew that neurons fire in patterns and that the pattern, the area and the types of neurons themselves are important, without being able to pinpoint why. The advent of optogenetics has allowed us to understand the role of specific brain regions and neurons in particular brain functions.
With optogenetics, we can investigate which neurons fire, in what pattern, and where.
For instance, if we believe that the CA3 region of the hippocampus is essential for memory formation (something we’ve actually known for a while), we can inactivate it in mice, and see if they can still perform tasks which require memory (they cannot).
Optogenetics has opened so many doors.
It has been used to cure epilepsy, reduce chronic pain, restore sight, cure symptoms of Parkinson’s disease and treat hearing loss. However, so far, most of the research has been restricted to rodents.
Scientists have even shown that activation of certain dopaminergic neurons (the reward system for the body) can drive certain behaviours, and this has clear implications for pleasure related activities in depression.
Optogenetics has also been used to understand brain wave patterns in mouse models of schizophrenia and autism spectrum disorders, and this will help us gain insight into the information processing troubles in humans. Scientists have even been able to implant false memories in the brains of mice!
The findings have huge implications for humans.
Optogenetics is already being used in clinical trials of Parkinson’s disease and retinal blindness. The main challenge before the technique is how to get humans to express these genes. Creating transgenic humans isn’t really an option, so we must rely on viruses, but challenges remain. Viruses must be implanted without spurring an immune response, and must be integrated into adult human neurons and produce the desired protein indefinitely.
In Parkinson’s disease, the region of the brain that malfunctions is the basal ganglia, a structure that’s critical for movement and coordination. Neurons in one part of the basal ganglia (substantia niagra or SN) are so damaged that their output isn’t as much as it should be. While there is already a technique in place to restore activity in this brain region, it’s highly invasive, among other shortcomings. With optogenetics, light stimulation could normalise activity of only the SN and thus restore normal motor function. We have also seen immense potential in curing retinal blindness. Clinical trials have commenced and we hope to see partial vision restorations in the patients.
We have made fair progress but there’s still a long way to go. The technique has a lot of promise, and is a testament to how much we can learn from nature. Karl Deisseroth, one of the inventors of the technique says:
“In classic microbial opsin work, we find meaning for the modern world — not just for science, but also for medicine and psychiatry — that makes a strong and clear statement for environmental protection, for preservation of biodiversity and for the pure quest for understanding. And the journey of optogenetics shows that hidden within the ground we have already traveled over or passed by, there may reside the essential tools, shouldered aside by modernity, that will allow us to map our way forward. Sometimes these neglected or archaic tools are those that are most needed — the old, the rare, the small and the weak.”
