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CU researchers pioneer new brain imaging technique

Process may allow scientists to capture neural activity in active, not restrained, subject

Brendan Heffernan works on a stimulated emission depletion (STED) microscope.
Brendan Heffernan works on a stimulated emission depletion (STED) microscope.

Researchers at the University of Colorado Boulder and Anschutz campuses have broken new ground by providing a proof of concept that adapting lasers through fibers and a powerful DIY microscope can track the brain activity of a free-moving subject.

“If we want to continue improving as a society, we need to know how the brain works,” said Brendan Heffernan, a PhD student at CU Boulder who headed the optical side of the project. “We could use this to see something in the brain we haven’t before.”

Neuroscientists use stimulated emission depletion (STED) microscopes to track the dendritic spines on neurons, which are tied to how the brain learns and develops. But they often run into two major roadblocks: access to the instruments and accurately reading an active brain.

Those powerful microscopes are often priced too high for laboratories. A 2016 article on priced Nikon Instruments’ N-SIM E at $600,000. Scientists and researchers who have access to laboratories that can afford the microscopes, or who instead settle for less powerful ones, then run into a problem just as daunting as any price tag: It’s difficult to track synapses when a subject is restrained.

“The only way to understand what the brain is doing is tracking it as it’s behaving and learning,” said Emily Gibson, an associate professor in the bioengineering department at CU Denver who collaborated on the project. “A lot of behaviors cannot be done in a restrained environment,”

Solving both the problem of cost and the problem of trying to image an active brain is what makes Heffernan’s project groundbreaking. He and four other researchers in the CU network built a STED microscope with off-the-shelf and commercially available parts, making it much less expensive than microscopes that are currently available, while also using fibers that can move with doughnut-shaped lasers — something that can deem other instruments as the static counterparts of yesteryear.

Stephanie Meyer, senior researcher at CU Anschutz; CU Anschutz professor Diego Restrepo; University of Denver professor Mark Siemens; and CU Boulder associate professor Juliet Gopinath are the other team members.

Nature Research journal Scientific Reports published the team’s proof of concept on July 31.

Essentially, the current process of tracking the synapses on cells can be equated to a single photo, whereas this process is the equivalent of a feature film. That motion picture, according to CU Boulder associate professor Zoe Donaldson, can offer a revolutionary look at the anatomy of learning in animals, including humans. In turn, access to that process can help prevent degenerative diseases.

“We don’t know the early stages of Alzheimer’s, a disease where you begin to lose your memory,” Donaldson said. “Are you losing synapses early or later? In theory, this can tell us what happens first.”

Heffernan, Gibson, and Restrepo all said that their breakthrough could help the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative. The initiative aims to achieve the mountainous task of understanding and preventing brain diseases like Alzheimer’s. While the team’s research doesn’t complete that initiative, it offers a tool that could be important to its work.