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From left: Diego Restrepo, Emily Gibson, Juliet Gopinath and Victor Bright.

Researchers from the and the have won a $2 million grant allowing them to refine a unique microscope they have developed while expanding its use to other scientists across the country.

“We will deploy a fiber-coupled, two photon miniature microscope to the laboratories of four users studying neural activity to understand vocal learning, decision making, social interactions and neural development in various species,” said Diego Restrepo, professor of cell and developmental biology and director of the Center for NeuroScience at the University of Colorado School of Medicine.

Restrepo along with Emily Gibson, assistant professor of bioengineering at CU Anschutz, Juliet Gopinath, associate professor in electrical, computer and energy engineering at CU Boulder and Victor Bright, professor of mechanical engineering at CU Boulder have collaborated on the development of the microscope and share the grant. CU Anschutz’s Baris Ozbay also helped create the microscope.

The $2 million grant, spread over three years, comes from the National Institutes of Health (NIH) and the National Institute of Neurological Disorders and Stroke (NINDS). It is part of the NIH’s new BRAIN Initiative aimed at revolutionizing the understanding of the human brain.

It goes to researchers developing innovative technologies that show how individual cells and complex neural circuits interact in both time and space. That knowledge will hopefully lead to cures, treatments and prevention of brain disorders.

The microscope, known as the 2P-FCM, uses an electrowetting lens mounted on the head of a live mouse where a high-powered, fiber optic light can actually view and control neural activity as it happens. The lens is liquid and can change shape when electricity is applied.

Gibson said the microscope is unique because it allows deeper brain imaging by using two-photon excitation with longer wavelengths to reduce light scattering in tissue.  

“Our 2P-FCM is the only miniature, head-mounted microscope that provides dynamic focus capability in real time to image different brain areas and cells in different layers of the brain to get a more complete picture of neuron interactions,” she said. “This grant will allow us to take our proof-of-concept design that we have demonstrated in my lab and begin to disseminate it for widespread use in the neuroscience community.”

Bright and Gopinath at CU Boulder spearheaded the development of the electrowetting lens.

“My group developed fluid-based, electrowetting tunable optical components for focusing and scanning the laser beam in the microscope,” Bright said.  “I have been working with Juliet Gopinath on the tunable fluid-based optics for eight years. We started working on the microscope concept with Diego Restrepo and Emily Gibson about five to six years ago.”

Gopinath has focused on the design and characterization of the adaptive optical elements that allow for 3-D imaging.

“I think that the technology I develop will actually be used to benefit society and have a direct impact on quality of life,” she said. “I also think this intersection of neuroscience and engineering is wonderful.”

The grant will allow the researchers to incorporate new holographic optogenetic stimulation into the microscope to record and modulate brain activity in awake animals.

It also offers four other scientists the chance to use the microscope to study neural activities in animals besides mice:

• Richard Mooney, professor of neurobiology at Duke University, will study the neural basis of vocal learning in songbirds.
• Bijan Pesaran, associate professor of neuroscience at New York University, will examine decision making in non-human primates.
• Ethan Hughes, assistant professor of cell biology at CU Anschutz, will study the dynamics of myelination. Myelin protects neurons and helps them conduct signals more efficiently.
• Zoe Donaldson, assistant professor behavioral neuroscience - molecular, cellular and developmental biology at CU Boulder, will investigate the neural basis of social bonding among prairie voles.

Last year, the team received a $600,000 grant from the National Science Foundation to use the microscope to reconnect neural communication between parts of the brain where it had been severed.

The Denver company 3i (Intelligent Imaging Innovations, Inc.) is working on the commercial release of the microscope.

The BRAIN Initiative grant number is U01 NS099577.