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The findings raise the possibility of using noninvasive methods for stimulating the brain to treat Parkinson’s patients, which Deisseroth and collaborators are now exploring. Transcranial magnetic stimulation (TMS), a way to activate parts of the brain using a magnet placed over the scalp, has already been approved by the Food and Drug Administration to treat depression. But studies using TMS to treat Parkinson’s have yielded mixed results, probably because “people have been poking around different parts of the brain, not being guided by this kind of knowledge,” says Deisseroth. In a new study, the researchers will first use sophisticated brain-imaging methods to try to identify in Parkinson’s patients the human correlate of the spot identified in animal studies–the exact area will likely vary from person to person–and then target the stimulation specifically to that region.

Scientists are also using optogenetics to study depression, another disease that can be treated with electrical stimulation. They hope to tease out the brain areas responsible for the different symptoms associated with depression, such as fatigue, hopelessness, and lack of pleasure in daily activities.

Researchers mimic clinical depression in mice by subjecting them to several days of extreme social stress. After such stress, these normally social animals refrain from social interaction for the rest of their lives. Like clinical depression in humans, this impairment generates abnormal patterns of neural activity in part of the brain called the prefrontal cortex, and it can be alleviated with antidepressants.

Herbert Covington, a researcher in Eric Nestler’s lab at Mount Sinai School of Medicine, in New York, made neurons in the prefrontal cortex of stressed mice sensitive to light. He then stimulated the animals’ neurons using light delivered in a pattern similar to that seen in healthy mice exploring a new environment. Much like antidepressants, the light treatment made the previously fearful animals socialize normally with other mice.

“Depression is a complex mix of behaviors,” says Covington. “Stimulating the prefrontal cortex can restore a social behavior. Next we will look at whether it can restore activity–will mice choose to do things they find rewarding, which is often a problem in depression.” The findings might ultimately enable researchers to develop treatments targeting specific aspects of the disease.

It’s not yet clear whether optogenetics technology will become a treatment itself or whether its major impact will be shedding light on disease. Two groups are already focusing on potential treatments: Ed Boyden at MIT has founded a startup to use optogenetics to restore sight to people with vision disorders by making damaged retinal cells sensitive to light, and a startup spun out of Case Western Reserve University in Cleveland, OH, plans to commercialize the technology to restore bladder control in paralyzed people.

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Credit: Karl Deisseroth

Tagged: Biomedicine, memory, diseases, optogenetics, Parkinson's, deep brain stimulation, depression

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