Dana News E-Blast: February

Here are some stories recently posted on dana.org

Cerebrum-February 2016-Lithium-Article ContentLithium to the Rescue

by Richard S. Jope, Ph.D., and Charles B. Nemeroff, M.D., Ph.D.

New research reveals lithium’s role as a neuroprotector and suggests that enzymes modulated by lithium could lead to new treatments for Alzheimer’s, Parkinson’s, multiple sclerosis, and other neurodegenerative disorders. From Cerebrum, our online magazine of ideas.

New Clues to the Causes of Bipolar Disorder

Cell and animal models point to abnormalities in two brain areas. Continue reading

Optogenetics: Controlling the Brain with Light

Photo source/credit: Ed Boyden/McGovern Institute for Brain Research at MIT

Photo source/credit: Ed Boyden/McGovern Institute for Brain Research at MIT

What if we could suddenly cease cravings caused by addiction or turn off feelings of depression with the flip of a switch? To better understand “one of the hottest areas of neuroscience research,” the American Association for the Advancement of Science (AAAS) welcomed three guests to discuss the latest developments in the field of optogenetics. The June 9th event was the latest in a series of luncheon briefings on Capitol Hill, hosted by AAAS and funded by the Dana Foundation.

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Emerging Techniques to Study the CNS

paul kenny christie fowler brian lee
Paul J. Kenny, Christie Fowler, and Brian Lee

In the June Report on Progress, Drs. Christie D. Fowler, Brian Lee, and Paul J. Kenny explain the use of two emerging techniques, optogenetics (light) and DREADDs (drugs), to better study how the central nervous system works.

The ability to manipulate the activity of specific subsets of neurons in the brains of living animals is leading to significant new insights into how the central nervous system works. The recently developed yet already well-established approaches of optogenetics and pharmacosynthetics use light or small molecules, respectively, to control the activity of neurons in the brains of laboratory animals. Using these techniques, we can see how distinct groups of neurons contribute to normal behavioral states or to abnormal behavior similar to those associated with neuropsychiatric disorders.

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–Blayne Jeffries

Lights on, brain off

If you’re a night owl like me, then those first rays of
sunshine in the morning often seem to make you feel even groggier than you did
when you went to bed. But scientists have found a new, efficient way to use
simple beams of light to literally—not just metaphorically—shut down the brain.

Ed Boyden, a research
professor at the Massachusetts Institute of Technology, and his colleagues have
discovered two new light-sensitive proteins that, when implanted into neurons,
prevent those cells from activating in the presence of certain wavelengths of
light. Arch, found in a species of bacteria, is sensitive to yellow light,
whereas Mac is of fungal origin and responds to blue light, the scientists
report
in the Jan. 7 issue of Nature.

Arch
A mouse neuron expressing Arch

These proteins, Boyden says, will not only provide
scientists with a powerful but reversible way to study specific brain regions,
but may also provide promising new gene therapy treatments for diseases caused
by overactive brain cells. One of the most drastic examples of such a disorder
is epilepsy,
in which spontaneous activity by neurons can sometimes spread throughout the
entire brain, causing violent seizures and occasionally death.

These aren’t the first light-sensitive proteins, or opsins,
that neuroscientists have adapted to their purposes. For some time, researchers
have been using opsins to both selectively activate and inhibit brain cells, a
field known as optogenetics. As we reported last month,
such techniques allow scientists to study the function of specific brain cells,
such as those involved in memory or disease, with greater detail and precision
than previously possible.

Opsins work because they are ion channels; when activated,
they allow charged particles into a cell. In the case of ChR2, blue light
causes an influx of charged particles that mimic what naturally occurs when a
neuron is told to fire. Halorhodopsin, on the other hand, adds chloride ions to
a cell’s interior that make it unable to send a signal. Halorhodopsin, however,
quickly becomes inactive in the presence of light, whereas the new proteins,
which allow protons into cells, “reset” themselves and can shut off cells for
very long periods of time. “These are an order of magnitude better,” Boyden
says. “They allow for near-digital turning off of neurons in awake animal
cortexes.”

In the Nature
paper, Boyden and his colleagues demonstrate the use of Arch and Mac in awake
mice, but he says that the team has also conducted tests in nonhuman primates
with no apparent side effects yet.  They
are also “very eager” to begin studying prototype therapies in mouse models for
epilepsy, chronic pain, brain injuries, and other brain diseases, he adds.
Opsins are normally implanted using gene therapy, in which a retrovirus is used
to insert the opsin-producing gene into the relevant brain cells. In recent
years, scientists have significantly improved their gene therapy techniques—for
instance, they can now target the right cells by altering the protein coat of
the virus or by adding different DNA promoter regions to the implanted
gene—Boyden says, and thus the risk of side effects such as cancer has dropped
dramatically.

Another benefit of the new long-lasting proteins, he adds,
is that scientists can now precisely and reversibly shut off small regions of
the brain to study their roles in activities like cognition and attention—essentially,
a “high-throughput scan for the brain.” Previously, scientists have obtained this
information largely by looking at lesions, but these are relatively large and
haphazard and provide no information about timing. “It’s like pulling the power
cord of a laptop. You don’t know if it’s the lack of a power or the processing
input causing the problem,” Boyden says. “We believe this will have a
significant effect on neuroscience.”

—Aalok Mehta

Image courtesy of Brian Chow, Xue Han and Ed Boyden / MIT

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