The Weekly Beaker: Optogenetics: a potential solution to depression, addiction and more

Optogenetics is a newly developed procedure used to control individual or groups of nerve cells in the brains of living creatures. By simply shining a light, optogenetics can activate or inhibit neurons with light-sensitive proteins, effecting radical cognitive or behavioral changes in the brain.

In 2002, researchers discovered the protein responsible for allowing green algae to swim to or from light, a unit called a channelrhodopsin. When a certain color of light, particular to each protein, contact the channelrhodopsin, the protein changes shape, opens up and allows ions to flow in. This is similar to the way nerve cells allow electrical signals to be generated, which forms the basis of thought and movement.

By isolating the gene for the channelrhodopsin and injecting it into specific areas of the mouse brain, the protein could take hold in neurons’ membranes. From there, just a touch of light was needed. Researchers attached an optic cable to the mice’s heads that allowed pulses of light to be delivered, resulting in control over the group of neurons’ activity. Channelrhodopsins activate cells but similar proteins called halorhodopsins inhibit cells. Essentially, the activity of these different proteins turns cells either on or off.

The applications of this technique are far-reaching. In addiction to cocaine, for example, the brain’s pleasure center receives a surge of activity upon exposure to the drug. But mice treated optogenetically with inhibitory halorhodopsins never experienced the addiction-forming pleasure spike, thus eliminating the addictive effects of cocaine.

Anxiety and depression are also conditions that may be within the realm of possible improvement by optogenetic techniques. The amygdala is known to be involved in fear and anxiety and by targeting the right circuits linking to the amygdala and stimulating them optogenetically, researchers increased exploratory behavior in mice—a sign of alleviated anxiety. What’s more, by stimulating a brain area called the medial prefrontal cortex, depressed mice showed signs of improved social contact, maze running and appetite—signs of alleviated depression. Optogenetics is a more targeted and faster approach than drugs, which take weeks to kick in and affect vast regions of the brain, rather than specific groups of neurons.

Narcolepsy, a psychiatric disorder where people fall asleep upon certain cues at inopportune times, can be disruptive and devastating. But by shining light on certain neurons the hypothalamus that control the cycle of sleep and wakefulness, narcoleptic animals can be signaled to stay awake. Parkinson’s is an equally distressing motor disorder where movement progressively becomes slower and shakier. But researchers were able to recover normal movement in Parkinsonian mice by stimulating a particular pathway of the neurons involved in the disease.

I’m sure you’ve noticed that I’ve qualified every important advance so far with the preface “in mice.” Human applications are 5 to 10 years away. And though the use of optogenetics in the brain can have fantastic implications, the first human uses will probably involve other slightly less complex, and thus less risky, organs. One possibility is using timed bursts of light to synchronize heart cell contractions—a new and improved pacemaker. Another is implanting light-sensitive proteins into vision cells of the blind and engineering glasses that shine light into them, restoring at least a rudimentary form of sight.

The diverse functionality of this technique won it the Method of the Year award in 2010 by Nature Methods, a science methodology journal. But as usual, this exciting technological and scientific breakthrough brings with it philosophical and ethical responsibilities. By learning which cells control which behavior, neuroscientists are probing the neural basis of what it means to want something, and how the basic switching on or off of neurons mediates amazingly complex behaviors like pursuing a goal or reflecting on oneself. If one can control behavior by controlling neurons, it becomes imperative to ensure the technology not be used for the wrong reasons. But for now, this development remains a magnificent harbinger of the futuristic ways that we can improve the lives of the ill.