High-Speed Microscope May Offer Insight into Autism, Schizophrenia

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High-Speed Microscope May Offer Insight into Autism, Schizophrenia

By TRACI PEDERSEN Associate News Editor

Reviewed by M. Grohol, Psy.D. on January 13, 2011

Certain brain disorders, such as schizophrenia, autism and mental retardation

are thought to be caused by a malfunction in brain cell communication and have

no easy-to-detect physical signs leading to diagnosis. In fact, even fMRIs and

PET scans are able to offer only limited detail of brain activity in these

cases.

Now neuroscientists at the University of California, Los Angeles (UCLA) have

joined forces with physicists to develop a non-invasive, extremely high speed

microscope that instantly captures the firing of thousands of neurons in the

brain as they communicate — or in these cases — miscommunicate with one another.

“In our view, this is the world’s fastest two-photon excitation microscope for

three-dimensional imaging in vivo,” said UCLA physics professor Dr. Katsushi

Arisaka, who developed the optical imaging system with Dr.

Portera-Cailliau, UCLA assistant professor of neurology and neurobiology, and

colleagues.

Since neuropsychiatric diseases like autism, schizophrenia and mental

retardation do not usually display any physical brain damage, they are believed

to be caused by conductivity problems — neurons not firing properly. Normal

cells have patterns of electrical activity, said Portera-Cailliau, but irregular

cell activity as a whole doesn’t create useful information the brain can use.

“One of the greatest challenges for neuroscience in the 21st century is to

understand how the billions of neurons that form the brain communicate with one

another to produce complex behaviors,” he said.

“The ultimate benefit from this type of research will come from deciphering how

dysfunctional patterns of activity among neurons lead to devastating symptoms in

a variety of neuropsychiatric disorders.”

Recently, Portera-Cailliau had been using calcium imaging, a method in which

neurons take up fluorescent dyes. When the cells fire, they “blink like lights

in a Christmas tree,” he said. “Our role now is to decipher the code that

neurons use, which is buried in those blinking light patterns.”

However, says Portera-Cailliau , that technique has its limitations.

“The signal of the calcium-based fluorescent dye we used faded as we imaged

deeper into the cortex. We couldn’t image all the cells,” he said.

Also, Portera-Cailliau and his team believed they were missing important

information because they couldn’t capture a big enough section of the brain fast

enough to measure the group-firing of individual neurons. That was the key

factor that drove Arisaka and Cheng, one of his graduate students, to

seek a faster method of recording neurons.

The microscope they developed is a multifocal two-photon microscopy with

spatio-temporal excitation-emission multiplexing (STEM). It is a modified

version of two-photon laser-scanning microscopes that record fluorescent calcium

dyes inside the neurons, but with the main laser beam split into four smaller

beams.

This technique lets them record four times more brain cells than the original

version, four times faster. Also, a different beam was used to record neurons at

various depths inside the brain, giving the image a completely novel 3-D effect.

“Most video cameras are designed to capture an image at 30 pictures per second.

What we did was speed that up by 10 times to roughly 250 pictures per second,”

Arisaka said. “And we are working on making it even faster.”

The result, he said, “is a high-resolution three-dimensional video of neuronal

circuit activity in a living animal.”

Portera-Cailliau is already reaping the benefits of this imaging technique in

his studies of Fragile X syndrome, a form of autism. Using this new technology,

he is able to compare the cortex of a normal mouse with a Fragile X mutant

mouse, and witness the misfiring of neurons in the Fragile X brain.

The study can be found in the Jan. 9 edition of the journal Nature Methods.