AURORA, Colo. – Researchers from the University
of Colorado Anschutz Medical Campus and the University of Colorado Boulder
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, PhD, 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, PhD, assistant
professor of bioengineering at CU Anschutz, Juliet Gopinath, PhD, associate
professor in electrical, computer and energy engineering at CU Boulder and
Victor Bright, PhD, professor of mechanical engineering at CU Boulder have
collaborated on the development of the microscope and share the grant. CU
Anschutz’s Baris Ozbay, PhD, 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
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
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
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.