The
spinal cord is harder to access and study than even the brain. The challenges
posed by its mobility and anatomical structure have made understanding exactly
how it functions difficult.
Rice
University engineers will work with collaborators to optimize an array of nanoelectronicthreads, or NETs⎯ already used
successfully for gathering high-fidelity, long-term data from neurons in the
brain ⎯ for use in the
spine, supported by a $6.25 million, four-year grant from the National Institutes of Health.
In
addition to neuronal activity recordings, NET probes can provide tunable,
localized stimulation of adjacent neurons. Rice neuroengineers also hope to
maximize NET’s functional bandwidth by integrating them into a larger-scale,
data-processing system.
The new
tool could help neuroscientists crack the secrets of spinal cord function and
bring new hope to patients dealing with injuries and other associated medical
conditions.
“So far,
we haven't had a good understanding of how the neurons in the spinal cord
actually work,” says Chong Xie, the principal investigator on the grant and an associate professor of
electrical and computer engineering and neuroengineering. “For example, if you
move your arms or walk around, you have the intention in your brain and the
muscles operate exactly as you want them to. This conversion of the initial
intention into specific motions of each of the muscles is operated and
implemented in the spinal cord, where circuits consisting of many, many neurons
are responsible for carrying out this job. But we don't know exactly how this
is achieved.”
Using
electrodes to track neuronal activity in the brain has allowed neuroscientists
to learn a great deal about brain function. The flexible NET probes developed
by Xie and collaborators integrate seamlessly with brain tissue and perform
better than rigid probes when used to record electrical information from
individual neuronsin the brain.
Preliminary
tests have shown that NET probes can achieve high-quality, long-duration
recordings from spinal cord neurons of mice. However, the scientists intend to
further adapt NETs to the specific structural and functional demands of the
spinal cord.
In the
brain, the distribution of neurons, or gray matter, and the bundles of nerve fibers known as white matter is the exact inverse of spinal cord anatomy.
“We
typically refer to this as the ‘inside-out anatomy’ of the spinal cord,” says Lan Luan, an assistant professor of electrical and computer engineering and
co-investigator on the grant. “The outer layer of the brain ⎯ the gray matter ⎯ is where the
neurons are, whereas the fibers called white matter are on the interior. In the
spinal cord, the white matter or fibers are on the exterior, shielding the
neurons. This makes accessing those neurons more challenging.”
To ensure
better access, scientists plan to develop a probe design that is small enough
to be implanted at different sites on the spine yet has greater depth coverage
and enough channels to capture data from neurons in a spinal cord cross
section.
Another
goal is to equip the probes with stimulation capabilities in addition to their
recording function.
“The
electrode can do both,” Luan says. “This has a direct health relevance, because
for patients with spinal cord injury or other types of injuries, stimulation
could be a way to restore fine motor control. There are several very successful
technologies demonstrating that stimulation in the cord can restore local
motions. But to impact finer motor control, we believe we need to go inside the
cord and have a greater degree of access and precision for applying this
stimulation.”
The
spinal cord plays a significant role in pain processes, so identifying which
spinal neurons are directly involved with pain-signal relay could open the door
to better pain-management therapies.
“Identifying
the specific type of spinal neurons that play a significant role in processing
pain information could potentially enable the development of drugs that target
precisely those cells,” Xie says. “Or maybe we can use the electrodes to
stimulate those neurons and modulate their activity so that they don’t convey
the pain signal to the brain.”
Scientists
plan to not only optimize probe design, but also to incorporate spinal NETs into
an extremely miniaturized, integrated data-processing and stimulation-feedback
system.
In
addition to developing the technology, Xie, Luan and their team have partnered
with the Pfafflab at the Salk Institute for Biological Studies, the Weberlab at Carnegie Mellon University and the Basbaum and
Ganguly labs
at University of California, San Francisco for a series of spinal cord studies
that will test the devices across different spinal regions, animal models and
research topics.
Luan said she hoped that developing and optimizing NET-based technology for
spinal cord research would “provide a tool that can help the entire
neuroscience community achieve a more fundamental understanding of spinal cord
function.”
“My real
hope is that, four years down the road, at the end of this project,
neuroscientists will be able to see and do new things that are impossible with
current technology,” Xie says.
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