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  • A 3-D light switch for the brain

Mar 2013

CAMBRIDGE, Mass. – A new tool that delivers precise points of light to living brain tissue in three dimensions could one day help treat Parkinson’s disease and epilepsy; it could even aid in the understanding of consciousness and how memories form.

Biologists and engineers at MIT developed the three-dimensional “light switch” using optogenetics. The method, only a few years old, sensitizes select brain cells to a particular color of light. By illuminating precise areas of the brain, scientists can selectively activate or deactivate the individual neurons that have been sensitized.

A scanning electron microscope image of the 3-D array with close-up of a single light-emitting probe. The close-up reveals several light ports along the probe’s edge. Images courtesy of A.N. Zorzos, J. Scholvin, E.S. Boyden and C.G. Fonstad/Optics Letters.

Optogenetics allows scientists to play a more active role in probing the brain’s connections, to fire up one type of cell or deactivate another and then observe the effect on a behavior, such as quieting a seizure. “You can see neural activity in the brain that is associated with specific behaviors, but is it important?” said Ed Boyden, a synthetic biologist at MIT and a pioneer in the field of optogenetics. “Or is it a passive copy of important activity located elsewhere in the brain? There’s no way to know for sure if you just watch.”

Entire circuits within the brain can now be explored with the new 3-D tool, which so far has been tested on mice. The 3-D array is precise enough to activate a single kind of neuron, at a precise location, with a single beam of light; previous techniques did not have the same precision. Probes delivering electricity to the brain could manipulate neurons, but they cannot target individual kinds of cells, Boyden said. Drugs can turn neurons on or off, but not on such a quick time scale, nor with such a high degree of control.

An optical image of the 3-D array with individual light ports illuminated. The array looks like a series of fine-toothed combs laid next to each other with their teeth pointing in the same direction.

A previous version of Boyden’s device looked like a needle-thin probe with light-emitting ports along its length; these ports allowed scientists to manipulate neurons along a single line. The new tool contains up to 100 probes – each just 150 µm across – in a square grid; the device looks like a series of fine-toothed combs laid next to each other with their teeth pointing in the same direction.

By adding a third dimension to the light-delivery capabilities, researchers can make any pattern of light they want within the volume of a cubic centimeter of brain tissue, using a few hundred independently controllable illumination points. The implants do not cause any discomfort because the brain lacks pain receptors.

Scientists sensitize the neurons with opsins, light-detecting proteins naturally found in bacteria and algae. Different colors of light turn on different opsins, and an individual neuron’s response depends on the type of opsin used and the light’s wavelength, giving neuroscientists unprecedented control over individual neurons in the brain.

The findings appeared in Optics Letters [doi: 10.1364/ol.37.004841].

A discipline that combines optics and genetics to enable the use of light to stimulate and control cells in living tissue, typically neurons, which have been genetically modified to respond to light. Only the cells that have been modified to include light-sensitive proteins will be under control of the light. The ability to selectively target cells gives researchers precise control. Using light to control the excitation, inhibition and signaling pathways of specific cells or groups of cells...
The technology of generating and harnessing light and other forms of radiant energy whose quantum unit is the photon. The science includes light emission, transmission, deflection, amplification and detection by optical components and instruments, lasers and other light sources, fiber optics, electro-optical instrumentation, related hardware and electronics, and sophisticated systems. The range of applications of photonics extends from energy generation to detection to communications and...
Acronym for profile resolution obtained by excitation. In its simplest form, probe involves the overlap of two counter-propagating laser pulses of appropriate wavelength, such that one pulse selectively populates a given excited state of the species of interest while the other measures the increase in absorption due to the increase in the degree of excitation.
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