On April 2, 2013, President Obama announced the launch of the Brain Research through Advancing
Innovative Neurotechnologies project or BRAIN and his intent to help “get this
project off the ground” by proposing significant investment on this project by
the National Institutes of Health (NIH), the National Science Foundation (NSF),
and the Defense Advanced Research Projects Agency (DARPA) in the budget he will
send to Congress next week. The new initiative will focus on developing and
improving new technologies to better understand the human brain at both a basic
level and at an applied level. The project builds on an early proposal
published in Science and co-authored by UCLA’s Paul Weiss, Director of
the California NanoSystems Institute, Fred Kavli Chair in NanoSystems Sciences,
and a distinguished professor in the departments of chemistry and biochemistry
and materials science and engineering, in which the program was called the
Brain Activity Map (BAM) project.
"Top nanoscientists and
neuroscientists have come together to see how the substantial investment and
advances in nanoscience and nanotechnology can be used to measure the dynamic
chemical and voltage signals in neural circuits." Weiss says. "This project
will enable us to develop and to test new models to understand processes such
as learning and memory. We may also be able to shed light on what causes
neurological disorders when brains malfunction."
The
brain is made up of an estimated 85 billion neurons connected at 100 trillion
junctures called synapses that dynamically transmit signals in response to
external or internal stimulation. Neurons communicate using both electrical signals,
such as the movement of ions to create voltage gradients across cell membranes,
and chemical signals, such as the release of neurotransmitters like serotonin
that diffuse across synapses between neurons. Moreover, sets of neurons work
together in networks or neural circuits to carry out different brain processes
and to provide signaling feedback.
Understanding
how these signals interact will likely depend on understanding neurons, not at
the individual level, but at the circuit level. These circuits can involve as
many as millions of individual neurons, making them extremely challenging to
study.
This
challenge is where the BRAIN Project comes in.
An
interdisciplinary group of nanoscience and neuroscience researchers from around
the country including Weiss; Anne Andrews, the Richard Metzner Endowed Chair in
Clinical Neuropharmacology, a Professor in the departments of psychiatry and
biobehavioral sciences and chemistry and biochemistry and member of CNSI and
the Semel Institute for Neuroscience & Human Behavior; and Sotiris
Masmanidis, Assistant Professor in the department of neurobiology and CNSI
member, have been designing methods to create maps of brain activity that measure
and probe the chemical and electrical signals involved in brain circuits.
"This
work is what I came to UCLA to do,” says Masmanidis, an expert in the
development of microscale neural probes, “to develop nanoscale tools to probe
the network-level dynamics of the brain at small scales and high speeds. In
order to do this, we have to make many simultaneous measurements beyond what is
currently possible."
Unlike
other attempts to map the static architectures of the brain—the framework of
neurons and their connections—this effort will build on previous knowledge to focus
on the dynamic signals that navigate through that framework. In an interview by
io9, George Church, a professor in the
department of genetics and the Wyss Institute at Harvard Medical School and co-author
of the Science perspective, compared
the difference to studying the distribution of a city’s telephone wires versus studying
“where, when, and how those wires are transmitting messages.”
"The
brain is a dynamic organ, a transducer between the body and the environment,
and as such it is constantly changing. To measure and to understand the dynamics
of the brain at a critical scale—looking simultaneously at the chemical,
physical and neurophysiological interaction among many thousands of neurons—is
a technically formidable challenge, for any perturbing analysis itself brings
further dynamic change. But we are beginning to assemble the tools that can
make such investigation possible and ultimately lead to better understanding of
disease and its treatment," says Peter Whybrow, Director of the Semel Institute
for Neuroscience and Human Behavior, Judson Braun Distinguished Professor and
Executive Chair of the Department of Psychiatry and Biobehavioral Sciences, and
Physician-in-Chief of the Stewart and Lynda Resnick Neuropsychiatric Hospital
at UCLA. "[BRAIN] is the compelling project for the science of our time."
The
project aims to provide valuable information that explains how actions,
thoughts, and emotions are controlled by the brain and seeks to shed light on
disorders such as Alzheimer’s disease, depression, and schizophrenia. Chemical and
voltage activity maps could also enable scientists to develop new therapeutic
drugs for such disorders.
"Understanding
the interacting, dynamic chemistry of the brain is the key to understanding,
and eventually treating, diseases such as anxiety and depression," says
Andrews. "My group teamed up with nanoscientist Paul Weiss a decade ago in
order to see how we might develop new tools to reach the smaller and faster
time scales at which the action happens."
The
timeliness of the initiative is based on the availability and coalescence of new
technology that will have a critical impact on the field. As the name of the
initiative implies, technology development will be a major driving force behind
the research.
An
article describing the current and possible future technologies for the project
and how they will enable this endeavor was recently published in ACS Nano by over two dozen co-authors including Andrews,
Masmanidis, Church, and Weiss, who is also the journal’s Editor-in-Chief.
"The
idea is to accelerate, by decades, the development and application of
technology to study the brain by bringing to bear the advances generated by the
major U.S. and international investments in nanotechnology over the last
decade," Weiss says.
Current
technology is capable of measuring either the electrical activity of a small number
of neurons at high resolution or of imaging the whole brain at relatively low-resolution,
but tools capable of working between those two extremes—focused on neural circuits—are
still in the early stages of development.
As
described above, tiny probes are being designed that are capable of recording
electrical signals over three-dimensional space within the brain. Novel optical
tools are being combined with computational approaches to improve the precision
of neural imaging while also increasing the numbers of neurons that can be
visualized simultaneously. Wireless electronic circuits can be introduced into
neuronal networks to measure activity and to affect signaling without requiring
invasive surgery.
Additionally,
the work of Weiss and Andrews has been focused on uncovering the relationships
between neurotransmitters and their receptors, chemical interactions that have
required the development of novel strategies that take advantage of cutting
edge chemical patterning technology, which enables the researchers to precisely
position receptors in a way that is optimized to identify their binding partners.
Experiments
will depend on the ability to work at micrometer and nanometer scales that will
enable the study of individual neural circuits, synapses between neurons, and
neurotransmitter receptors.
Comparisons
between the BRAIN project and the Human Genome Project have been drawn. The
Human Genome Project, formally begun in 1990 and coordinated by the U.S.
Department of Energy and the National Institutes of Health (NIH), energized researchers
and catalyzed discussion leading to new areas of investigation. The main goals
of the project were to identify all of the genes in human DNA and to determine
the sequences of the 3 billion chemical base pairs that make up human DNA. Approximately
$300 million per year was provided for the effort.
Likewise,
BRAIN offers a new opportunity for collaboration among the NIH, the NSF, and DARPA,
with room for participation from industry and foundations. If all goes well,
the return from the BRAIN project will rival the return—estimated by some to be
$140 for every $1 spent—coming from the Human Genome Project. The project will
also create additional jobs for individuals trained in multiple fields and
provide educational enrichment, both from a scientific standpoint and from a technology
training standpoint. Ethical implications of the research will also be
required, according to the White House.
"We
have a chance to improve the lives of, not just millions, but billions of
people on this planet through the research that’s done in this BRAIN initiative
alone,” Obama said in his announcement. “But it’s going to require a serious
effort, a sustained effort, and it’s going to require us as a country to embody
and embrace that spirit of discovery that is what made America America."
Reprinted from the CNSI website.
