Georgia Tech graduate student Jeffrey Stirman, School of Chemical & Biomolecular Engineering associate professor Hang Lu, and graduate student Matthew Crane (left-right) have designed an inexpensive illumination technology to stimulate and silence specific neurons and muscles of freely moving worms, while precisely controlling the location, duration, frequency and intensity of the light. (Credit: Gary Meek)
Researchers are using inexpensive components from ordinary liquid crystal
display (LCD) projectors to control the brain and muscles of tiny organisms,
including freely moving worms. Red, green, and blue lights from a projector
activate light-sensitive microbial proteins that are genetically engineered
into the worms, allowing the researchers to switch neurons on and off like
light bulbs and turn muscles on and off like engines.
Use of the LCD technology to control small animals advances the field of
optogenetics—a mix of optical and genetic techniques that has given researchers
unparalleled control over brain circuits in laboratory animals. Until now, the
technique could be used only with larger animals by placement of an optical
fiber into an animal’s brain, or required illumination of an animal’s entire
A paper published in the advance online edition of the journal Nature Methods describes how the inexpensive
illumination technology allows researchers to stimulate and silence specific
neurons and muscles of freely moving worms, while precisely controlling the
location, duration, frequency, and intensity of the light.
“This illumination instrument significantly enhances our ability to control,
alter, observe and investigate how neurons, muscles and circuits ultimately
produce behavior in animals,” said Hang Lu, an associate professor in the School
of Chemical & Biomolecular Engineering at the Georgia Institute of
Lu and graduate students Jeffrey Stirman and Matthew Crane developed the
tool with support from the National Institutes of Health and the Alfred P.
The illumination system includes a modified off-the-shelf LCD projector, which
is used to cast a multi-color pattern of light onto an animal. The independent
red, green and blue channels allow researchers to activate excitable cells
sensitive to specific colors, while simultaneously silencing others.
Researchers at Georgia Tech use light from an LCD projector to directly control the muscles of an immobilized worm. (Credit: Hang Lu)
“Because the central component of the illumination system is a commercially
available projector, the system’s cost and complexity are dramatically reduced,
which we hope will enable wider adoption of this tool by the research
community,” explained Lu.
By connecting the illumination system to a microscope and combining it with
video tracking, the researchers are able to track and record the behavior of
freely moving animals, while maintaining the lighting in the intended
anatomical position. When the animal moves, changes to the light’s location,
intensity and color can be updated in less than 40 milliseconds.
Once Lu and her team built the prototype system, they used it to explore the
“touch” circuit of the worm Caenorhabditis elegans by exciting and
inhibiting its mechano-sensory and locomotion neurons. Alexander Gottschalk, a
professor in the Johann Wolfgang Goethe-Univ. Frankfurt Institute of
Biochemistry in Frankfurt, Germany, and his team provided the
light-sensitive optogenetic reagents for the Georgia Tech experiments.
For their first experiment, the researchers illuminated the head of a worm
at regular intervals while the animal moved forward. This produced a coiling
effect in the head and caused the worm to crawl in a triangular pattern. In
another experiment, the team scanned light along the bodies of worms from head
to tail, which resulted in backward movement when neurons near the head were
stimulated and forward movement when neurons near the tail were stimulated.
Georgia Tech researchers illuminate the head of a worm expressing light-sensitive optogenetic reagents. The light produces a coiling effect in the head and causes the worm to crawl in a triangular pattern. (Credit: Hang Lu)
Additional experiments showed that the intensity of the light affected a
worm’s behavior and that several optogenetic reagents excited at different
wavelengths could be combined in one experiment to understand circuit
functions. The researchers were able to examine a large number of animals under
a variety of conditions, demonstrating that the technique’s results were both
robust and repeatable.
“This instrument allowed us to control defined events in defined locations
at defined times in an intact biological system, allowing us to dissect animal
functional circuits with greater precision and nuance,” added Lu.
While these proof-of-concept studies investigated the response of C.
elegans to mechanical stimulation, the illumination system can also be
used to evaluate responses to chemical, thermal and visual stimuli. Researchers
can also use it to study a variety of neurons and muscles in other small
animals, such as the zebrafish and fruit fly larvae.
“Experiments with this illumination system yield quantitative behavior data
that cannot be obtained by manual touch assays, laser cell ablation, or genetic
manipulation of neurotransmitters,” said Lu.