Summary: A
new 3D electrode array allows researchers to map the activity and
location of up to 1 million synaptic links in a living brain.
Source: Rice University
It’s
a mystery how human thoughts and dreams emerge from electrical pulses
in the brain’s estimated 100 trillion synapses, and Rice University
neuroengineer Chong Xie dreams of changing that by creating a system
that can record all the electrical activity in a living brain.
In a recently published study in Nature Biomedical Engineering,
Xie and colleagues described their latest achievement toward that goal,
a 3D electrode array that allows them to map the locations and activity
of up to 1 million potential synaptic links in a living brain based on
recordings of the millisecond-scale evolution of electrical pulses in
tens of thousands of neurons in a cubic millimeter of brain tissue.
“The
thing that is novel about this work is the recording density,” said
Xie, an associate professor of electrical and computer engineering at
Rice and a core member of the Rice Neuroengineering Initiative.
“Microcircuits
in the brain are very mysterious. We don’t have many ways to map their
activity, especially volumetrically. We want to deliver very dense
recordings of the cortex because those are important, scientifically,
for understanding how brain circuits work.”
Xie
collaborated on the study with colleagues from Rice and the University
of California, San Francisco, including Loren Frank of UCSF and
co-corresponding author Lan Luan of Rice.
Neurons
are small. Each cubic millimeter of brain tissue contains about
100,000. That density is roughly the same for humans and other mammals,
including the rodents that are the subject of experiments in Xie’s lab.
The
processing power of the brain arises from synaptic connections between
neurons. Synaptically linked neuron pairs are connected by narrow
bridges of tissue called axons, which are just a few millionths of a
meter in diameter.
Xie’s
team has spent years developing a material called nanoelectronic thread
(NET) that is thin, ultraflexible and biocompatible, a trifecta of
properties for making minimally invasive electrode implants. In previous
studies, Xie’s team has demonstrated techniques for emplanting tightly
packed NET arrays of up to 128 electrodes.
The
researchers also showed their arrays could stay in place for up to 10
months, recording the pulsed spikes of electricity, or action
potentials, in nearby neurons.
“When
neurons fire action potentials, there are very faint electrical signals
coming out of them,” Xie said. “You have to place the electrodes very
close to each neuron in order to capture that signal. Usually, that
means a distance less than 100 microns.”
Using
electrodes to record neuronal spikes has been a primary technique in
neuroscience for decades, but the evolution of electrode materials has
gradually transformed the implantation of neural electrodes from highly
invasive procedures that damaged the very brain tissue the electrodes
were meant to measure to procedures that result in no measurable tissue
damage.
One
of the primary focuses of Xie’s lab is scaling up the size of its
implant arrays. In the new study, Xie and colleagues, including Hanlin
Zhu, one of the lead graduate students on the project, implanted arrays
of 1,024 NET electrodes in a 1 cubic millimeter volume of brain tissue.
“The
primary signals we try to measure are the electrical spikes coming from
neurons,” Xie said. “That’s how they communicate. And one thing we care
a lot about and really want to understand is how neurons are
connected.”
Xie said there is no straightforward way to probe synaptic connections.
“Axons
can be very long, and each neuron can be connected by many thousands of
others,” he said. “It’s a very, very, very messy network. And probing
it is an extremely challenging task, especially while the brain is
working.”
The
density of the new electrode array, together with its ability to
capture millisecond-by-millisecond changes in the electrical spikes of
individual neurons allowed Xie and co-authors to decipher potential
synaptic links between neuron pairs.
“When the synapse works, you usually see a typical pattern when you look at the firing activity of the two neurons,” Xie said.
It
takes a bit of time for the electrical impulse that starts in the
presynaptic neurons to propagate down the axon and activate the
postsynaptic neuron, he said.
“We
record many, many spikes, and then we need to sort the spikes and
attribute each of them to individual neurons,” he said. “We know the
location of each electrode, or channel. And each channel records no more
than a few neurons at a time. Each neuron is also typically recorded by
more than one contact as well. So, you can do something akin to
triangulation to identify the location of individual neurons.”
Once
the neurons are mapped, it’s relatively easy to calculate the distance
between them and from that, the propagation time for synaptic
activation.
The
1,024-electrode array gave Xie’s team a ratio of approximately one
electrode per 100 neurons in the cubic millimeter volume of brain tissue
under study. The lab is working to create denser arrays that pack more
electrodes into the same volume.
The
vast majority of neurons in people’s brains are unused, despite the
fact that our brains typically consume about as much energy as can be
supplied by the body. Neuroscientists don’t fully understand why the
brain has so many unused neurons, and Xie said that’s a factor his team
considers in the design of their electrode arrays.
“I
want to capture as much of the interactivity as possible,” he said. “I
would argue that we don’t need a 1-to-1 ratio of electrodes to neurons
to capture all of it, and it is indeed my dream to capture all the
interactivity.”
About this neuroscience research news
Author: Jade Boyd
Source: Rice University
Contact: Jade Boyd – Rice University
Image: The image is in the public domain
Original Research: Closed access.
“Ultraflexible electrode arrays for months-long high-density electrophysiological mapping of thousands of neurons in rodents” by Zhengtuo Zhao et al. Nature Biomedical Engineering