ENHANCED: Optogenetics


Brain control has always proven tricky, particularly when it comes to the brain trying to control itself. We have many indirect methods — drugs, meditation, education, travel, etc. — but people have always wanted quick and reliable control of their brain states. And what that actually means is that they want to change an area of the brain. Switching the drives and mental states we need on and off would be considerably less frustrating than the transitioning struggles nature has given us. And so we are entering the era of a new set of technologies for direct neural control.

The best current technology combines psychosurgery and implantation. Right now, hard-to-treat disorders can get a difficult direct neural treatment called Deep Brain Stimulation, or DBs. DBs is like a pacemaker for the brain. An electrode is snaked down to the area associated with the disorder being treated and left in place. After the surgery has healed, the implant pulses current at a frequency that either activates or quiets the area responsible for the condition. Affecting cells further from the electrode means passing more current through nearby cells. DBs is by far the most precise clinical procedure for controlling areas of the brain, but it’s still disappointingly non-specific. Since DBs involves brain surgery, it’s generally a treatment of last resort, but it’s shown good results for previously untreatable cases of Parkinson’s, chronic pain, and depression. Electrode implantation is an extreme measure, not likely to be widely used.

Dr. Karl Deisseroth of Stanford University can go one better. He’s developed a technique called optogenetics that combines genetic engineering, lasers, neurology and surgery to create a direct control mechanism. Optogenetics uses a brain cell switch with two genetic parts. The first is a gene taken from an algae that activates the cell in the presence of blue light in order to turn towards the light and photosynthesis. In a neuron, that activation fires the cell. The second is from an archaeon, a salt-based extremophile, which responds to yellow light by pumping chlorideions. In a brain cell, that means not firing at all.


OptogeneticsTo get the genes in place, Deisseroth’s team opens up the skull and uses a pipette to apply a nonreproducing adenovirus to the desired brain area. The virus is genetically configured to inject both genes into a single cell type. The single cell will take both genes. After the “light switch” genes are in place, those brain cells are now light sensitive and a 50 micrometer fiber optic cable is fed to the area. In this way, they can target very specific deep brain structures, areas currently too deep and fragile for most psychosurgery. Once the researcher attaches the other end of the cable to a laser, he or she has absolute and flawless control over that group of neurons: blue light on, yellow light off.

Dr. Deisseroth is a psychiatrist as well as bioengineer, and he envisions using optogenetics in place of DBs’s not-so-deep cousin, Vagus Nerve Stimulation. Much like DBs, VNs uses an electrode to treat depression and epilepsy but targets where the vagus nerve passes through the neck rather than deep in the brain. It can still cause problems in many patients — sleep apnea, throat pain, coughing, and voice changes are the main complaints. Deisseroth believes optogenetics might be a way of reducing the side effects of VNs by targeting the treatments, rather than just shocking the neck region.

All this points to easier and more effective neural control. We’re still far from knowing which cells do what, and further from orchestrating treatments and enhancements for specific conditions. But for the first time we can map and build useful handles on the very things that make us ourselves.

Quinn Norton covers science, technology, law and whatever else gets her attention. she lives in Washington D.C. and is most easily reachable at quinn@quinnnorton.com

Leave a Reply