A Wiring Diagram of the Brain
In the following article, the authors explain how scientists would like to understand the wiring diagram of
the brain but that with current techniques it would take a very long time. They go on to show new ways
of doing that job that involve bouncing electrons off the top of a block of brain tissue to generate a
cross-sectional picture of the nerve fibers in that slice. They then take a very thin slice off the top of the
block and repeat the process. By doing this, they can develop a three dimensional diagram of the
interconnections in the brain. This new field of study is called connectomics and methods to automate
the process are being developed. The rate of progress in this field is similar to the rate of progress in
decoding DNA, which has been very rapid.
The emerging field of connectomics could help researchers decode the brain's approach to information
processing. http://www.technologyreview.com/biotech/19731/?a=f
By Emily Singer
Analyzing axons: Scientists are developing new ways to study the tangled web of neurons in the brain.
This image shows a partial reconstruction of the rabbit retina. Neural projections, which connect neuron
to neuron, are labeled in different colors.
New technologies that allow scientists to trace the fine wiring of the brain more accurately than ever
before could soon generate a complete wiring diagram--including every tiny fiber and miniscule
connection--of a piece of brain. Dubbed connectomics, these maps could uncover how neural networks
perform their precise functions in the brain, and they could shed light on disorders thought to originate
from faulty wiring, such as autism and schizophrenia.
"The brain is essentially a computer that wires itself up during development and can rewire itself," says
Sebastian Seung, a computational neuroscientist at MIT. "If we have a wiring diagram of the brain, that
could help us understand how it works." For example, scientists previously identified the part of the
songbird's brain that is important in the birds' ability to generate songs. Seung would ultimately like to
develop a wiring diagram of this structure in order to elucidate the features underlying its unique
capability.
Only one organism's wiring diagram currently exists: that of the microscopic worm C. elegans. Despite
containing a mere 302 neurons, the C. elegans mapping effort took more than a decade to complete, in
the 1970s. It has been an invaluable research resource and earned its creators a Nobel Prize.
With an estimated 100 billion neurons and 100 trillion synapses in the human brain, creating an
all-encompassing map of even a small chunk is a daunting task. Using standard methods, it would take
roughly three billion person years to generate the wiring diagram of a single cortical column, a narrow
functional unit of neurons in the cortex, estimates Winfried Denk, a neuroscientist at the Max Planck
Institute for Medical Research in Heidelberg, Germany.
Denk, Seung, and their collaborators are now developing sensitive new imaging techniques and
machine-learning algorithms to automate the construction process. They have already generated a
partial wiring diagram of part of the rabbit retina. But they'll need to make their technique a million times
faster to finally bring larger maps--like that of a cortical column--into the realm of reality.
Previous efforts to map the wiring of the brain have focused on larger anatomical features, such as the
thick wiring tracts that connect different parts of the brain, or on the paths of single neurons, stained a
particular color to distinguish them from their tangled multitude of neighbors. But to truly understand
how a network of neurons can perform a particular function, scientists need a new kind of map. "A lot of
properties of brain function are at the level of the circuit--information is being integrated, processed,
extracted," says Elly Nedivi, a neuroscientist at MIT who is not involved with the research. "To
understand what that means, you need to be able to see who connects to whom."
Denk and his colleagues developed a new technique to make more fine-scaled wiring maps using
electron microscopy. Starting with a small block of brain tissue, the researchers bounce electrons off the
top of the block to generate a cross-sectional picture of the nerve fibers in that slice. They then take a
very thin--30-nanometer--slice off the top of the block and repeat the process. Scientists go through the
images slice by slice to trace the path of each nerve fiber. "Repeat this [process] thousands of times,
and you can make your way through maybe the whole fly brain," says Denk.
Seung and Denk aim to dramatically speed up the tracing process, which takes a single graduate
student weeks to complete, with automated machine-learning algorithms. The researchers use data
from a manually generated wiring diagram to train an artificial neural network to emulate the human
tracing process. They can then use the resulting algorithm to analyze new chunks of brain tissue. To
date, they've been able to speed the process about one hundred- to one thousand-fold. The
researchers presented their initial findings to an awed crowd at the Society for Neurosciences meeting
in San Diego earlier this month. They showed the three-dimensional reconstruction of part of the rabbit
retina called the inner plexiform layer, which is a piece of neural tissue at the back of the eye that
senses light and sends visual information to the brain. (See a movie of the reconstruction here.) "But we
need to improve 106-fold or more," says Denk, who estimates that this would shrink the three billion
person years it would take to trace a cortical column down to about two years. "I'm confident in the end
that we will be able to do it," he says. "But I don't know how long it will take us--if we're lucky, maybe a
year or so." Earlier this month, scientists at Harvard described a new method of tracing neurons in the
living brain by labeling them with up to a hundred different colors. (See "The Technicolor Brain.") "We're
starting to think about wiring diagrams as being fundamental," says Jeff Lichtman, one of the
researchers who developed the technique. Researchers say that the two approaches will likely be
complementary, allowing scientists to look at neural circuits of different dimensions. Eventually, Seung
aims to generate maps of the complete fly connectome, as well as partial wiring diagrams of interesting
locations in larger brains, such as the hippocampus, olfactory bulb, and retina. Just exactly how much
light these maps will shed on the brain is still somewhat controversial. "Just knowing the [wiring] data
won't take us far if we don't put it in the framework of processing and transferring data in the brain,"
says David van Essen, a neuroscientist at Washington University, in St. Louis, and president of the
Society for Neurosciences. Seung and others eventually hope to generate maps that incorporate the
biochemical and physiological properties of various cells into the wiring diagrams.
Next
In the following article, the authors explain how scientists would like to understand the wiring diagram of
the brain but that with current techniques it would take a very long time. They go on to show new ways
of doing that job that involve bouncing electrons off the top of a block of brain tissue to generate a
cross-sectional picture of the nerve fibers in that slice. They then take a very thin slice off the top of the
block and repeat the process. By doing this, they can develop a three dimensional diagram of the
interconnections in the brain. This new field of study is called connectomics and methods to automate
the process are being developed. The rate of progress in this field is similar to the rate of progress in
decoding DNA, which has been very rapid.
The emerging field of connectomics could help researchers decode the brain's approach to information
processing. http://www.technologyreview.com/biotech/19731/?a=f
By Emily Singer
Analyzing axons: Scientists are developing new ways to study the tangled web of neurons in the brain.
This image shows a partial reconstruction of the rabbit retina. Neural projections, which connect neuron
to neuron, are labeled in different colors.
New technologies that allow scientists to trace the fine wiring of the brain more accurately than ever
before could soon generate a complete wiring diagram--including every tiny fiber and miniscule
connection--of a piece of brain. Dubbed connectomics, these maps could uncover how neural networks
perform their precise functions in the brain, and they could shed light on disorders thought to originate
from faulty wiring, such as autism and schizophrenia.
"The brain is essentially a computer that wires itself up during development and can rewire itself," says
Sebastian Seung, a computational neuroscientist at MIT. "If we have a wiring diagram of the brain, that
could help us understand how it works." For example, scientists previously identified the part of the
songbird's brain that is important in the birds' ability to generate songs. Seung would ultimately like to
develop a wiring diagram of this structure in order to elucidate the features underlying its unique
capability.
Only one organism's wiring diagram currently exists: that of the microscopic worm C. elegans. Despite
containing a mere 302 neurons, the C. elegans mapping effort took more than a decade to complete, in
the 1970s. It has been an invaluable research resource and earned its creators a Nobel Prize.
With an estimated 100 billion neurons and 100 trillion synapses in the human brain, creating an
all-encompassing map of even a small chunk is a daunting task. Using standard methods, it would take
roughly three billion person years to generate the wiring diagram of a single cortical column, a narrow
functional unit of neurons in the cortex, estimates Winfried Denk, a neuroscientist at the Max Planck
Institute for Medical Research in Heidelberg, Germany.
Denk, Seung, and their collaborators are now developing sensitive new imaging techniques and
machine-learning algorithms to automate the construction process. They have already generated a
partial wiring diagram of part of the rabbit retina. But they'll need to make their technique a million times
faster to finally bring larger maps--like that of a cortical column--into the realm of reality.
Previous efforts to map the wiring of the brain have focused on larger anatomical features, such as the
thick wiring tracts that connect different parts of the brain, or on the paths of single neurons, stained a
particular color to distinguish them from their tangled multitude of neighbors. But to truly understand
how a network of neurons can perform a particular function, scientists need a new kind of map. "A lot of
properties of brain function are at the level of the circuit--information is being integrated, processed,
extracted," says Elly Nedivi, a neuroscientist at MIT who is not involved with the research. "To
understand what that means, you need to be able to see who connects to whom."
Denk and his colleagues developed a new technique to make more fine-scaled wiring maps using
electron microscopy. Starting with a small block of brain tissue, the researchers bounce electrons off the
top of the block to generate a cross-sectional picture of the nerve fibers in that slice. They then take a
very thin--30-nanometer--slice off the top of the block and repeat the process. Scientists go through the
images slice by slice to trace the path of each nerve fiber. "Repeat this [process] thousands of times,
and you can make your way through maybe the whole fly brain," says Denk.
Seung and Denk aim to dramatically speed up the tracing process, which takes a single graduate
student weeks to complete, with automated machine-learning algorithms. The researchers use data
from a manually generated wiring diagram to train an artificial neural network to emulate the human
tracing process. They can then use the resulting algorithm to analyze new chunks of brain tissue. To
date, they've been able to speed the process about one hundred- to one thousand-fold. The
researchers presented their initial findings to an awed crowd at the Society for Neurosciences meeting
in San Diego earlier this month. They showed the three-dimensional reconstruction of part of the rabbit
retina called the inner plexiform layer, which is a piece of neural tissue at the back of the eye that
senses light and sends visual information to the brain. (See a movie of the reconstruction here.) "But we
need to improve 106-fold or more," says Denk, who estimates that this would shrink the three billion
person years it would take to trace a cortical column down to about two years. "I'm confident in the end
that we will be able to do it," he says. "But I don't know how long it will take us--if we're lucky, maybe a
year or so." Earlier this month, scientists at Harvard described a new method of tracing neurons in the
living brain by labeling them with up to a hundred different colors. (See "The Technicolor Brain.") "We're
starting to think about wiring diagrams as being fundamental," says Jeff Lichtman, one of the
researchers who developed the technique. Researchers say that the two approaches will likely be
complementary, allowing scientists to look at neural circuits of different dimensions. Eventually, Seung
aims to generate maps of the complete fly connectome, as well as partial wiring diagrams of interesting
locations in larger brains, such as the hippocampus, olfactory bulb, and retina. Just exactly how much
light these maps will shed on the brain is still somewhat controversial. "Just knowing the [wiring] data
won't take us far if we don't put it in the framework of processing and transferring data in the brain,"
says David van Essen, a neuroscientist at Washington University, in St. Louis, and president of the
Society for Neurosciences. Seung and others eventually hope to generate maps that incorporate the
biochemical and physiological properties of various cells into the wiring diagrams.
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