Optogenetics: Lighting Up the Brain

Inside our head is a raging electrical storm that creates the basis of our very existence. The electricity created by the cellular clouds controls our mood, movement, and thoughts, and we have little to say about how this storm rages on. But what if we could harness the lightning of our brain, and control what these cells say to each other? What if we can make our brains less anxious, less depressed, and more resistant to neurological diseases? The new science of optogenetics gives humans the tools needed to harness the power of the brain and control it with specificity that hasn’t been seen before, and all it takes is some genetic engineering and a little light.

To understand optogenetics, one first has to understand how the neurons talk with one another. Action potentials are the language of the brain’s cells allowing the brain to communicate complicated information between its regions. Communication of the brain has been a subject of research for the greater part of human history. But only relatively recently did Hodgkin and Huxley famously discover ion channels.

Ion channels are how the brain starts the electrical communication of action potentials. When a channel on a cell is opened, it allows in a spark that causes the cell to fire. The firing of a neuron causes an action potential to speed down the cell and communicate with its neighboring neurons. The discovery of these channels revolutionized neuroscience in the 1940s and 1950s, but it would be another 50 years before humankind could control the communication of the brain.

Neuroscience researchers throughout the 20^th century knew they could make a neuron fire with the use of electricity by mimicking the spark of an ion channel. However, this method posed challenges, as the electricity would activate multiple cells and ruin the specificity of the experiment. If more than one cell is made to fire at a time, it would be impossible to tell how any given neuron contributes to communication in the brain. The ability to isolate cells for activation is the key to finding out the purpose of each cell, and each brain region those cells make up.

One researcher in 1979 stated the need for technology that could control only one neuron and the potential that could have on future research. Little did he know, the beginning of that discovery was occurring during the same decade.

During the 1970s, scientists discovered proteins known now as opsins. The most famous of which was channelrhodopsin, found in green algae, and whose protein channel would open in response to blue light, much like an ion channel. When the protein channel opened, it allowed in charged ions which could cause an action potential to fire, forcing communication. This communication was cell-specific and would not impact the cells around it. The research into opsins was conducted into the 21^st century, where a study in 2005 combined the knowledge of opsins with the field of genetics.

In the 2005 paper, the researchers showed that they could successfully control the firing of a neuron by causing it to make its own opsin proteins, then activating that protein with light. The methods used by the researchers were revolutionary to the field of neuroscience and would become the standard for years to come.

In studies where individual cells were used, activation was easy, it was as simple as shining a light onto a petri dish. But later studies aimed to control the neurons inside test animals while they were still alive, and measure how they react. The surgical implementation of an optic fiber was placed inside the skull of a test animal and shined specifically in the area of the brain that possess the opsin proteins.

The implications of this initial study were massive, and the lead writers for the paper have won many awards for their work on optogenetics, including in the field of medicine. This is because optogenetics could have a huge impact on how we study brain diseases. With the mental health crisis in the world continually rising, we must discover new ways to study the diseases that plague the human mind.

For many years, the mechanism for mental health diseases has been ambiguously defined. For example, depression has something to do with serotonin, dopamine, and norepinephrine, but the exact mechanisms are still unclear. Optogenetics can be a great tool for uncovering the root cause of these common, yet elusive, neurological conditions.

A study in 2011 showed that using optogenetics, researchers could reverse depression-like symptoms in lab mice. They did this by shining light specifically onto neurons that release dopamine when fired. The idea is that increasing the pleasure of the mice, would in turn decrease the level of depression pathology. The researchers were successful in their approach and gained new insight into how dopamine is involved with depression. But more importantly, this research, and many others like it, raise the question of whether optogenetic technology may one day be available for human therapies.

The most likely candidate for human optogenetic therapy is in the treatment of Parkinson’s disease. Deep brain stimulation is already an accepted practice, where electrical impulses are sent into targeted areas of the brain to cause controlled firing of the neurons. Sounds familiar, doesn’t it?

The issue with deep brain stimulation mirrors problems encountered by early neuroscience researchers. Electrical impulses are not specific enough, and they could also activate surrounding tissue, which causes additional movement symptoms beyond the patient’s normal Parkinson’s symptomology.

Optogenetics could be the solution to this specificity problem. In one study, researchers showed that the activation of neurons using optogenetics was successful in reducing symptoms in a Parkinson’s mouse model.

The implications of these kinds of studies for science and medicine cannot be understated. Information gathered during these studies in mice gives us insight into diseases that have confounded scientists for decades. Along with this increased understanding, we are simultaneously developing a possible therapeutic solution to these problems in humans.

There may be one day, where a patient long-suffering from depression, Parkinson’s, or any neurological disease, will visit their doctor and get treated with a small beam of light instead of surgery or medication.

The science of optogenetics is shining new light on how we understand our brain and the diseases that plague it. The ability to use optogenetics could very well be one of the biggest discoveries in neuroscience research, and seeing what information it can bring us will be an anticipated event.