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An open-source technology called the optoclamp closes the loop in optogenetic systems. The technique uses a computer to acquire and process the neuronal response to optical stimulus and provides feedback control. Photo by Rob Felt.

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Optogenetics provides a powerful tool for studying the brain by allowing researchers to activate and suppress neurons using simple light-based signals. But until now, these optical stimulation techniques have been “open loop,” meaning they lack the kind of feedback control that most biological and engineering systems use to maintain a steady operating state.

Optogenetics technology places genes that express light-sensitive proteins into mammalian cells that normally lack such proteins. When the proteins are illuminated with specific wavelengths of light, they change the behavior of the cells. But without a feedback loop, scientists could only assume that the optical signals were having the effects desired.

To address that shortcoming, researchers have created an open-source technology called the optoclamp, which closes the loop in optogenetic systems. The technique uses a computer to acquire and process the neuronal response to the optical stimulus in real-time and then vary the light input to maintain a desired firing rate. By providing this feedback control, the optoclamp could facilitate research into new therapies for epilepsy, Parkinson’s disease, chronic pain — and even depression.

“Our work establishes a versatile test bed for creating the responsive neurotherapeutic tools of the future,” said Steve Potter, an associate professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University. “Neural modulation therapies of the future, whether they be targeted drug delivery, electrical stimulation, or even light-plus-optogenetics through fiber optics, will all be closed loop. That means they will be responsive to the moment-to-moment needs of the nervous system.”

Feedback control already exists for neural stimulation systems based on electrical inputs; the optoclamp will provide similar control for optical stimulation. The research, supported by the National Institutes of Health and the National Science Foundation, and including researcher Jon Newman, was published in the journal eLife.

— John Toon

Steve Potter

Steve Potter is an associate professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University. He develops neuroscience technologies for studying learning and memory in vitro.

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