See-through brains aid neuro research, foil zombies

Researchers can now get a literally clearer view of the workings of the brain, after a Stanford University neuroscientist found a way to replace opaque tissue with a gel-like substance.

 

Dr. Karl Deisseroth's technique is expected to give researchers a glimpse into the inner workings of the brain that can help them detect conditions like autism and Alzheimer's, the Sydney Morning Herald reported.  

"You can paint different wires different colors. We could see structures down to paired neurons on each side of a synapse," said Deisseroth, one of 15 experts on the team that will map out goals for US President Barack Obama's $100-million initiative to uncover the mysteries of the brain.

 

"(Studying intact brains) would give you a better chance of working out connections over large distances, which would help you determine structure-function relationships," he added. CLARITY  

Dubbed CLARITY, the technique replaces the opaque tissue in brains harvested from lab mice or donated by people for research with "hydrogel," a substance similar to contact lenses.

 

For the first time, one can see large structures such as the hippocampus, along with even neural circuits and individual cells.  

Dr. Francis Collins, director of the US National Institutes of Health, which helped fund the research, added CLARITY "has the potential to unmask fine details of brains from people with brain disorders without losing larger-scale circuit perspective."

 

Dr. Thomas Insel, director of the US National Institute of Mental Health, added the technique can "transform the way we study the brain's anatomy and how disease changes it."

 

"The in-depth study of our most important three-dimensional organ" will no longer be "constrained by two-dimensional methods" and the black box that is the brain could become downright luminous, he added.

 

Before CLARITY, scientists could trace neural connections only by cutting a brain into very thin slices, and examining each slice under a microscope.

 

However, such a technique risks deforming the tissue and makes it hard to map long-range connections.

 

Neuroscientist William Newsome, who will co-lead Obama's initiative, said the hydrogel technique is "a major technological innovation" that "will speed our mapping of the brain's 'circuit diagram.'"

 

Newsome said the mapping is "an essential goal of neuroscience, and will probably be a substantial focus" of Obama's brain project.

 

Biochemical engineering

 

The SMH article said the brain is opaque due to the fatty membranes that surround and support its cells.

 

Deisseroth and his team immersed the brains of three-month-old mice in a vat of the jelly-like hydrogel, whose molecules seeped into the brain and replaced the lipid bilayers.

 

The fatty membranes were then removed through an electro-chemical process.

 

With the hydrogel in place, the scientists heated it to just above body temperature. The molecules connected to one another and formed a sturdy mesh.

 

After eight days, the scientists had an intact, see-through mouse brain.

 

With CLARITY, the Stanford scientists could see the thalamus and the brainstem, the cortex and hippocampus with the naked eye.

 

A microscope allowed them to delve further, seeing white matter that serves as a brain's transmission lines that relay signals from one neuron to another.

 

Hydrogel bonus

 

As a bonus, the hydrogel is not only transparent but also permeable, allowing scientists to infuse special fluorescent dyes into the brain.

 

More importantly, the process worked on human brains, despite concerns that the use of preservatives such as formalin or formaldehyde might block the hydrogel process.

 

With the technique, the scientists clarified one healthy human brain and one autistic brain, the autistic one having been pickled for more than six years.

 

Yet even the pickled brain revealed "dendritic bridges", ladder-like connections within the brain's white matter that resemble those in Down syndrome. — TJD, GMA News