3D rendering of all ~140k neurons in the
fruit fly brain. Credit: Data source: FlyWire.ai; Rendering by Philipp Schlegel
(University of Cambridge/MRC LMB).
The
first wiring diagram of every neuron in an adult brain and the 50 million
connections between them has been produced for a fruit fly.
This landmark achievement has been
conducted by a large international collaboration of scientists, called the FlyWire Consortium, including researchers from the MRC Laboratory of
Molecular Biology (in Cambridge, UK), Princeton University, the University of
Vermont and the University of Cambridge.
It is published in a pair of
papers in Nature.
The diagram of all 139,255 neurons in the adult fly brain is the first of an entire brain for an animal that can walk and see. Previous efforts have completed the whole brain diagrams for much smaller brains, for example, for that of a fruit fly larva, which has 3,016 neurons, and a nematode worm, which has 302 neurons.
3D rendering of all ~140k neurons in the fruit
fly brain. Credit: Data source: FlyWire.ai; Rendering by Philipp Schlegel
(University of Cambridge/MRC LMB).
The researchers say the whole
fly brain map is a key first step to completing larger brains.
Since the fruit fly is a common tool in research, its brain map can be used to
advance our understanding of how neural circuits work.
Dr. Gregory
Jefferis, from the MRC Laboratory of Molecular Biology and from the University
of Cambridge, who was one of the co-leaders of the research, said, "If we
want to understand how the brain works, we need a mechanistic understanding of
how all the neurons fit together and let you think. For most brains, we have no
idea how these networks function.
"Flies
can do all kinds of complicated things like walk, fly, navigate, and the males
sing to the females. Brain wiring diagrams are a first step towards
understanding everything we're interested in—how we control our movement,
answer the telephone, or recognize a friend."
Dr. Mala
Murthy, from Princeton University, who was one of the co-leaders of the
research, said, "We have made the entire database open and freely
available to all researchers. We hope this will be transformative for
neuroscientists trying to better understand how a healthy brain works.
"In the
future, we hope that it will be possible to compare what happens when things go
wrong in our brains, for example in mental health conditions."
Brains are not snowflakes
The scientists
found that there were substantial similarities between the wiring in this map
and previous smaller-scale efforts which have mapped out parts of the fly
brain. This led the researchers to conclude that there are many similarities in
wiring between individual brains—that each brain isn't a unique structure like
a snowflake.
When comparing
their brain diagram to previous diagrams of small areas of the brain, the
researchers also found that about 0.5% of neurons have developmental variations
which could cause connections between neurons to be mis-wired. The researchers
say this will be an important area for future research to understand if these
changes are linked to individuality or brain disorders.
Making the map
A whole fly brain is less than 1 millimeter wide. The researchers started with one female brain cut into seven thousand slices, each only 40 nanometers thick, that were previously scanned using high resolution electron microscopy in the laboratory of project co-leader Davi Bock, then at Janelia Research Campus in the US.
3D rendering of the ~100 motor neurons
of the fruit fly brain. These neurons control the fly's mouth parts. The colors
correspond to the nerve they project through. Credit: Data source: FlyWire.ai;
Rendering by Philipp Schlegel (University of Cambridge/MRC LMB).
Analyzing
over 100 terabytes of image data (equivalent to the storage in 100 typical
laptops) to extract the shapes of about 140,000 neurons and 50 million
connections between them is too big a challenge for humans to complete
manually. The researchers built on AI developed at Princeton University to
identify and map neurons and their connections to each other.
However, the AI still makes many errors
in datasets of this size. The FlyWire Consortium—made up of teams in more than
76 laboratories and 287 researchers around the world, as well as volunteers
from the general public—spent an estimated 33 person-years painstakingly
proofreading all the data.
Dr. Sebastian Seung, from Princeton
University, who was one of the co-leaders of the research, said, "Mapping
the whole brain has been made possible by advances in AI computing—it would not
have been possible to reconstruct the entire wiring diagram manually. This is a
display of how AI can move neuroscience forward. The fly brain is a milestone
on our way to reconstructing a wiring diagram of a whole mouse brain."
The researchers also annotated many
details on the wiring diagram, such as classifying more than 8,000 cell types
across the brain. This also allows researchers to select particular systems
within the brain for further study, such as the neurons involved in sight or
movement.
Dr. Philipp Schlegel, the first author
of one of the studies, from the MRC Laboratory of Molecular Biology, said,
"This dataset is a bit like Google Maps but for brains: the raw wiring
diagram between neurons is like knowing which structures on satellite images of
the earth correspond to streets and buildings.
"Annotating neurons is like adding the names for streets and towns, business opening times, phone numbers, reviews, et cetera to the map—you need both for it to be really useful."
3D rendering of the 75k neurons in the
fly's visual system. Credit: Data source: FlyWire.ai; Rendering by Philipp
Schlegel (University of Cambridge/MRC LMB).
Simulating brain function
This is also the first whole brain
wiring map—often called a connectome—to predict the function of all the
connections between neurons.
Neurons use electrical signals to
send messages. Each neuron
can have hundreds of branches that connect it to other neurons. The points
where these branches meet and transmit signals between neurons are called
synapses. There are two main ways that neurons communicate across synapses:
excitatory (which promotes the continuation of the electrical signal in the
receiving neuron), or inhibitory (which reduces the likelihood that the next
neuron will transmit signals).
Researchers
from the team also used AI image scanning technology to predict whether each
synapse was inhibitory or excitatory.
Dr. Jefferis
added, "To begin to simulate the brain digitally, we need to know not only
the structure of the brain, but also how the neurons function to turn each
other on and off."
"Using
our data, which has been shared online as we worked, other scientists have
already started trying to simulate how the fly brain responds to the outside
world. This is an important start, but we will need to collect many different
kinds of data to produce reliable simulations of how a brain functions."
Associate
Professor Davi Bock, who was one of the co-leaders of the research, from the
University of Vermont, said, "The hyper-detail of electron microscopy data
creates its own challenges, especially at scale. This team wrote sophisticated
software algorithms to identify patterns of cell structure and connectivity
within all that detail.
"We can
now make precise synaptic level maps and use these to better understand cell
types and circuit structure at whole-brain scale. This will inevitably lead to
a deeper understanding of how nervous systems process, store and recall
information. I think this approach points the way forward for the analysis of
future whole-brain connectomes, in the fly as well as in other species."
This research was conducted using a female fly brain. Since there are differences in neuronal structure between male and female fly brains, the researchers plan to also characterize a male brain in the future.
Source: Researchers map the entire brain of an adult fruit fly for the first time (medicalxpress.com)
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