Frustrated by the extreme difficulty of rendering brain tissue transparent, bioengineering professor Karl Deisseroth of Stanford University tried a new approach. In addition to being a psychiatrist, he also has a long-term interest in the evolving field of optogenetics — growing light-sensitive proteins into specific types of brain cells. Deisseroth’s work since the early 2000s has involved taking tissue samples from the brain of a mouse, which he and his researchers place in a solution of hydrogels (light-sensitive fluid that could support and carefully insulate the neurons of given connections in the brain).
The solution binds to proteins and cross-linkers on contact and the researchers expose the tissue to normal human body temperature (98.6 degrees Fahrenheit), allowing a rubbery mesh to form that preserves the connections inside. Remaining unbound molecules are then washed out with a detergent and the samples can be stained for examination under a 3-D microscope. From there, the results can be graphed into a computer program, an intricate process that lets researchers build an entire construction of a brain over time.
In the near future, Deisseroth’s method of polymeric scaffolding — also known by the acronym CLARITY — may be used to bond to neurons within a live brain, giving imaging technology access to a transparent brain. Not only do psychiatrists stand to benefit, however. After looking at the stained neural circuits, Deisseroth’s team began compiling a model of the prefrontal cortex — that is the front portion of the frontal lobe, involved in planning and decision-making, an area known to significantly determine our personalities.
With a detailed map of the prefrontal cortex, neuroscientists and ethologists have a predictive model for what may trigger behavioral disorders like schizophrenia, autism, and dementia — three costly and debilitating disorders that we have yet to learn a great deal about. In a few years’ time, determining the causes and likelihood of mental illnesses could become as exact a science as predicting long-term weather patterns.
THE LIVING BRAIN
The CLARITY methods investigated by Deisseroth are far from the only options pursued by researchers across the globe. Juergen Knoblich, the deputy scientific director of the Institute of Molecular Biotechnology of the Austrian Academy of Sciences, in Vienna, has dedicated the last five years of research to developing organoids — a project he affectionately refers to as growing “brains on a dish.”
Knoblich and his colleagues targeted embryonic stem cells — cells that had yet to be genetically programmed with building instructions. They also isolated adult stem cells from genetically altered skin and blood cells. Within five days, the cells aggregate into an embryoid of three distinct layers, and are then placed in a droplet of Matrigel, a thick membrane made out of cartilage tumors isolated from mice. This provides the nutrients the cells need to continue dividing and to form small appendages, similar to flower buds, that will give rise to brain structures. Within a month, the buds will gradually develop into a fully formed forebrain — a structure similar to that of a 10-week-old embryo. A lab-grown brain sounds like the premise of a horror movie, but already these brains have proven invaluable in the wake of the Zika epidemic.
Labs in both the United States and Brazil identified nerve cells damaged by the mosquito-borne Zika virus using organoids. These same organoids could also be used in developing treatments against the disease. Neuroscientists could use the technique of tissues grown in culture to test new drugs, and in doing so, could eliminate the need for a great deal of animal testing. While the process seems to bring ethics under question, the organoids have no consciousness on their own and therefore cannot be considered sentient beings — and their benefits, which offer us a substantial degree of scientific advancement, far outweigh any potential harm.
This article was originally published in the Spring 2017 issue of Brain World Magazine.
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