Researchers at the Massachusetts Institute of Technology (MIT) have come up with a method for enlarging brain samples, allowing them to be studied more closely with less expensive equipment. To make the good news even better, the method is relatively simple, very inexpensive and uses chemicals that are commonly available.
Research on the human brain is currently a popular field. In 2013, President Obama announced $100 million in funding for the The Brain Research through Advancing Innovative Neurotechnologies, or BRAIN project. The project aims to reconstruct the activity of every single neuron in the brain.
Mapping the brain is no small project and $100 million may not be enough. Each of the 86 billion neurons in the human brain has between 1,000 and 10,000 synapses for a total of approximately 125 billion synapses, all of which relate in some way to complex human behavior and thought processes. To make matters worse each of these neurons and synapses is incredibly small and the equipment needed to study the human brain is both scare and expensive.
However, if the brain can ever be properly mapped and all of those synapses and neurons can be accounted for the payoff could be enormous. According to Brainmapping.org, “the purpose and goal of brain mapping is to advance the understanding of the relationship between structure and function in the human brain. Scientists in this field seek to gain knowledge of the physical processes that underlie human sensation, attention awareness and cognition. These results are immediately applicable to surgical intervention, to the design of medical interventions and to the treatment of psychological and psychiatric disorders.”
Now, in a paper published in the journal Science, researchers have found a way to make brain samples larger allowing the samples to be studied more closely with less expensive microscopes.
The current generation of “super-resolution” microscopes can look inside cells and have a resolution better than 250 nanometers. The MIT researchers have devised a method to study brain samples by making the samples larger instead of making the microscopes more powerful.
“Instead of acquiring a new microscope to take images with nanoscale resolution, you can take the images on a regular microscope. You physically make the sample bigger, rather than trying to magnify the rays of light that are emitted by the sample,” says Ed Boyden, an associate professor of biological engineering and brain and cognitive sciences at MIT in a statement.
Boyden’s method is called “expansion microscopy”, it involves using fluorescently-labelled antibodies that bind to specific proteins. These serve as a sort of map for labelling regions prior to the expansion. Next the sample is infused with a solution of commonly available chemicals, including sodium acrylate and then washed in salt-free water. This can result in a 100 fold expansion in volume, but because of the fluorescent labelling everything is still clearly defined.
“What you’re left with is a three-dimensional, fluorescent cast of the original material. And the cast itself is swollen, unimpeded by the original biological structure,” said Paul Tillberg, a graduate student who was lead author on the paper.
The discovery has the potential to allow more researchers to do more work using common and inexpensive chemicals rather than “super-resolution” microscopes.
“The exciting part is that this approach can acquire data at the same high speed per pixel as conventional microscopy, contrary to most other methods that beat the diffraction limit for microscopy, which can be 1,000 times slower per pixel,” said George Church, a professor of genetics at Harvard Medical School who was not part of the research team.
While this particular research focused on applications for brain tissue, Boyden believes that the same technique might be applied to other tissues and could help with the study of tumors and immune system responses.
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