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Optogenetics Controlling Brain Circuits with Light



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Optogenetics is a modern technology that enables researchers to precisely target and control specific events in biological systems, including freely-moving mammals. Gain or loss of function of well-defined biological activities in certain cells of living tissue is achieved by using a combination of genetic and optical methods.

This technology which has paved new ways for researchers to study specific biological functions has been developed by a neuroscientist and psychiatrist Karl Deisseroth and his colleagues at the Stanford University in 2005.

As a neuroscientist and psychiatrist, Deisseroth wanted to learn how various circuits in the brain affect behavior and what was amiss in the brains of his patients with schizophrenia and depression. To be able to do this more precisely without stimulating too many cells in the vicinity of the specific brain circuits they wanted to study, Deisseroth and his team inserted a gene for a photosensitive algal protein into mice brains, where it penetrated the nerve cells. When the modified nerve cells are exposed to light, by way of the fiber-optic implant, the protein stimulates electrical activity within the cell.

Basically optogenetics allows researchers to investigate unanswered questions about the brain, including the role of certain brain areas responsible for memory, addiction, and the sleep-wake cycle.

To render nerve cells sensitive to light, they are genetically engineered to express a protein adapted from green algae. When these modified nerve cells are exposed to light via the fiber-optic implant, the protein stimulates electrical activity within the cell that spreads to the next nerve cell in the circuit. Thus the researchers are able to control the activity of specific nerve circuits with millisecond accuracy and study the effects.

The technology of optogenetics was used by Michael Hausser and colleagues at University College London to probe the mechanism of memory storage in mice. By using genetic engineering techniques, the researchers made the light-sensitive protein to be expressed only in the nerve cells of the hippocampus that were triggered during the process of memory formation. Then they taught the mice to be scared of a certain sound by pairing it with an electric shock. The sound caused the animals to freeze in fear and stimulated the production of the protein in the activated neurons.

The following day, the researchers subjected the hippocamal tissues of the mice to blue light. This led to the activation of the specific cells that fired during memory formation the previous day, causing the mice to respond to light in fear, rather than to the sound. These cells were then labeled using a fluorescent marker which allows the researchers to quantify the number of cells involved in the formation of the memory.

Optogenetics has been used in advancing the basic scientific understanding of the effects of certain cell types on the function of neural circuits in vivo. The technology has also paved the way for studies to find key insights into Parkinson’s disease. In studying the brain circuits involved in this disease, Deisseroth and his team discovered that they could relieve the motor deficits in animals with Parkinson’s like symptoms by activating neural targets located nearer the surface of the brain.

Other recent studies using optogenetics provided insights into neural codes playing significant roles in various neurological and psychiatric disorders such as autism, schizophrenia, drug abuse, anxiety, and depression.

Herbert Covington, a researcher in Eric Nestler’s lab at Mount Sinai School of Medicine, in New York, used optogenetics to treat stressed mice. He genetically engineered nerve cells in the prefrontal cortex of stressed mice to become responsive to light. Then he activated the nerve cells of the mice by using light shone in a manner similar to that observed in healthy mice exploring a new environment. The light treatment caused the previously fearful animals to interact with other mice, much like antidepressants. These findings might eventually allow researchers to develop treatments that target specific aspects of the disease.

Although it is still unclear whether optogenetics will turn out to be a treatment itself or whether it will play a major role in providing a better understanding of a disease process, it has certainly become a very important technology in the field of neuroscience. The potential of this technology in the field of therapeutics is already being investigated by Ed Boyden at MIT, who worked with Deisseroth in the 2005 investigation. He has launched a startup to utilize optogenetics as a way of restoring eyesight to people with vision disorders by rendering damaged retinal cells responsive to light. 

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ARTICLE SOURCES AND CITATIONS
  • InfoBoxCallToAction ActionArrowhttp://2) http://www.stanford.edu/group/dlab/papers/breakthroughscience2010.pdf
  • InfoBoxCallToAction ActionArrowhttp://www.technologyreview.com/biomedicine/23767/page1/
  • InfoBoxCallToAction ActionArrowhttp://www.technologyreview.com/biomedicine/23767/page2/