Optogenetic Applications for Anxiety, Parkinson's Disease, and Pain

Optogenetics, turning nerve cells on and off by the exposing them to light, has a number of applications other than restoring sight to people who have retinitis pigmentosa. Among the optogenetic therapies in development are:

Anxiety 

Psychiatrist Karl Deisseroth was dissatisfied with the way medications worked for treating anxiety, so in 2004 in he founded a lab to study the use of light as a drug-free treatment for the condition. At first, many people were confused about what he doing. They thought he was studying the brain, using fiber optic cables to observe the brain. Actually he was doing therapy, changing the brain works, rather observing how it works.

Dr. Deisseroth and his collaborators chose a strain of mice known for its hiding abilities. These mice would spend most of their time in tiny spaces in the dark avoiding predators. He then genetically engineered the mice so that they had light-sensitive neurons in a region of the brain known as the amygdala, which enables mice (and humans) to process fearful experiences into long-term memories that help them avoid dangerous situations.

Next Deisseroth implanted a fiber optic cable into the brains of the mice to deliver blue light inside the amygdala. In this case, blue light "turned off" the brain cells associated with anxiety and mice that had clung to sides of their cages happily scampered around to look for food.

Parkinson's disease 

A universal problem in Parkinson's disease is that the medications used to treat it become less effective over time. It is almost as if these drugs cause parts of the brain to "flame out" and become insensitive to further medication, especially to dopamine. To combat this problem, some neurologists have started recommending implantable electrical stimulators that deliver a current to the brain to stop tremors or to restart coordinated motion.

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Dr. Alexxei Kravitz and colleagues at Stanford have been studying structures known as direct- and indirect-pathway medium spiny projection neurons (MSNs, for short) to see if light therapy might be a more effective way of treating the disease. The direct MSNs have one kind of dopamine receptor, and the indirect MSNs have another. Kravitz's team discovered that stimulating direct MSNs relieves Parkinson's, and stimulating indirect MSNs causes Parkinson's. (In other words, dopamine and medications to keep dopamine levels high stimulate some parts of the brain that improve symptoms and other parts of the brain that make symptoms worse, so medication inevitably fails.) Optogenetics may make it possible to stimulate just those neurons that enable normal motion without stimulating other neurons that interfere with it.

Chronic pain 

Scientists at McGill University in Montréal have found a way to genetically modify peripheral neurons, nerve cells outside the brain and spinal cord, so that they can be activated by light to defeat chronic pain. This method does not require any kind of brain surgery, and it completely avoids any side effects of painkilling drugs. However, to date, it has only been used in mice in the laboratory. Human trials are still some years away.