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The Discovery

How bacteria move toward and away from light

The study of obscure bacteria found in pond scum may not seem like the
quickest path to curing neurological disorders like Parkinson's disease. Yet
blue-green algae may hold the key to solving some of the most difficult
problems in neuroscience.


A Scientific Puzzle
For centuries scientists have studied single-celled organisms such as
bluegreen algae, puzzled by how they could sense and move toward and away
from light without eyes. Only within the past few years did researchers
discover that this movement was controlled by molecules called
channelrhodopsins, photosensitive molecules much like those found in the
retina of the human eye. Unlike molecules in the retina, however, these
channelrhodopsins can generate electrical signals directly that allow this
behavior in response to light.

An Unexpected Finding
Several independent research groups identified examples of these genes when
they were combing through a database of the blue-green algae genome and
noticed the similarity between retinal pigments and these molecules. Further
research suggested an amazing discovery: the new channelrhodopsins, in
addition to sensing light, might also function as ion channels - proteins
that allow charged particles to move into and out of cells and generate
electrical signals. In the nervous system, ion channels are essential to
transmit signals from one nerve cell to another.

The next exciting step was discovering that light can indeed open these
channels directly and thereby let ions flow in sufficient quantities to
excite brain cells, first tested simply in a dish in the laboratory.
Researchers then discovered related molecules that can turn cells off: one
extreme organism, salt-loving bacteria that grow in some desert lakes, has a
light-activated ion channel "pump" that could be used to shut cells down.

Together, these two light-activated channels - the channelrhodopsin and the
pump, one providing excitation and the second inhibition - provide exciting
new tools for controlling the electrical activity of neurons.

New Application
Activating neurons in living animals with light


Shortly after the discovery of channelrhodopsins, it occurred to researchers
that these new molecules could achieve a long-standing goal in neuroscience:
a non-invasive way to turn activity on or off in particular parts of our
brains.



Using modern genetic methods, light-activated channels can be added to
neurons that do not normally have them. This allows scientists to turn
neurons in a living brain on or off simply by exposing them to light.

Developing Therapies and Probing Brain Function
Studies in worms and other animals show that neurons or muscles made to
produce channelrhodopsins can be activated and deactivated quickly by light
in living animals, eliciting behaviors that previously had been produced
only by mechanical or electrical stimulation.

Research using light-activated channels in genetically-modified mice has
also shown the potential for developing therapies and for probing the
function of specific parts of the brain in mammals. For example, a study in
some types of blind mice found that responses to light could be restored
when channelrhodopsins were added to neurons in the inner retina. The
findings show that light can be used to precisely manipulate neural activity
in the living brain.

Light-activated channels also have the potential to advance our
understanding of brain function and circuitry. Neuroscientists will be able
to control the activity of specific groups of neurons remotely, with nothing
more than pulses of light. By activating or inactivating specific groups of
neurons, neuroscientists can understand how these neurons function in the
brain to produce particular behaviors.

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Health Implications
Better diagnosis and non-invasive techniques















With new technology, the light-activated channel discoveries can be used to
map neural circuitry with extreme precision, improving diagnosis and
offering new treatments.


In the future, the ability to activate or inactivate parts of the brain
noninvasively has the potential to revolutionize the understanding of a
number of neurological disorders, including those that arise because parts
of the brain are either too active or not active enough - such as Parkinson's
disease in which cells that make dopamine are lost, causing altered activity
levels in downstream circuits.

In the longer term, information gained about particular brain structures
involved in behavior, emotion, and cognition is likely to help scientists
design effective new treatment strategies for a number of brain disorders,
not only for Parkinson's disease but other neurological and psychiatric
disorders including epilepsy and depression.

Non-Invasive Treatments, Fewer Side Effects
Non-invasive treatment with light could reduce problems with the current
technologies for brain stimulation because the method is precise and fast.
For instance, some Parkinson's disease treatment involves the use of
electrodes implanted into particular brain regions. However, sometimes these
procedures can be ineffective, perhaps because the correct cell type is not
targeted, and can cause serious side effects to surrounding brain areas not
targeted for treatment.

Moreover, selective activation of targeted neurons would result in fewer
side effects. Unlike electrical stimulation, this method could be used on
genetically defined neuronal populations, which means that only the targeted
neurons would be affected.

Another exciting potential application is to design neural prosthetic
devices that use light to activate neurons that could take over the function
of a limb. Although a number of technical challenges still must be solved
before light-activated channels can be used effectively for these kinds of
therapeutic strategies, the potential uses are numerous.









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