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August 14, 2013

Scientists Use Light To Reach New Understandings of the Brain



optogenetics


 Brain Mapping
Scientists at Yale University have used a new protein, called ArcLight, to watch nerve cell electricity in a live fly brain. This new tool of optogenetics allows researchers to watch, in real time, the cell’s electrical activity.




Scientists have used fruit flies to show for the first time that a new class of genetically engineered proteins can be used to watch electrical activity in individual brain cells in live brains. The results, published in Cell, suggest these proteins may be a promising new tool for mapping brain cell activity in multiple animals.

 The research also has potential applications for studying how neurological disorders disrupt normal nerve cell signaling. Understanding brain cell activity is a high priority of President Obama’s Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative.

Brain cells use electricity to control thoughts, movements and senses. Ever since the late nineteenth century, when Dr. Luigi Galvani induced frog legs to move with electric shocks, scientists have been trying to watch nerve cell electricity to understand how it is involved in these actions.

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Usually they directly mo nitor electricity with cumbersome electrodes or toxic voltage-sensitive dyes, or indirectly with calcium detectors. This study, led by Michael Nitabach, Ph.D., J.D., and Vincent Pieribone, Ph.D., at the Yale School of Medicine, New Haven, CT, shows that a class of proteins, called genetically encoded fluorescent voltage indicators (GEVIs), may allow researchers to watch nerve cell electricity in a live animal.

Dr. Pieribone and his colleagues helped develop ArcLight, the protein used in this study. ArcLight fluoresces, or glows, as a nerve cell’s voltage changes and enables researchers to watch, in real time, the cell’s electrical activity.

“Electrical signals are the language the nervous system uses to transmit information,” says Pieribone, professor of cellular and molecular physiology and of neurobiology. “Now we can look at this electrical information optically and non-invasively.”
 In this study, Dr. Nitabach and his colleagues engineered fruit flies to express ArcLight in brain cells that control the fly’s sleeping cycle or sense of smell. Initial experiments in which the researchers simultaneously watched brain cell electricity with a microscope and recorded voltage with electrodes showed that ArcLight can accurately monitor electricity in a living brain.

Further experiments showed that ArcLight illuminated electricity in parts of the brain that were previously inaccessible using other techniques. Finally, ArcLight allowed the researchers to watch brain cells spark and fire while the flies were awakening and smelling. These results suggest that in the future neuroscientists may be able to use ArcLight and similar GEVIs in a variety of ways to map brain cell circuit activity during normal and disease states.

"Seeing electrical activity in the brain directly is a long-standing dream that now seems tangible,” says Gero A. Miesenböck, M.D., director of the Center for Neuronal Circuits and Behavior at the University of Oxford and a former associate professor of cell biology at the School of Medicine.

While at Yale, Miesenböck pioneered optogenetics, the use of light to control behavior via genetically encoded photosensitive components in neurons. What Pieribone, Nitabach, and colleagues have done is the flip side of optogenetics, using light, or fluorescence, to visualize neural activity, which Miesenböck calls “an important milestone.” While ArcLight is the most favorable GEVI available at the moment, says Miesenböck, a big challenge still remains in improving optical instrumentation for even better localization of neural signals in both space and time.

In the two videos below, fruit flies are shown without and with the ArcLight protein modification. The scientists simultaneously watched ArcLight glow and recorded the electricity of a brain cell with an electrode. The red and green traces at the bottom show that ArcLight glowed in parallel with changes in the cell's electricity (white trace).





SOURCE  Yale University

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