The connections within the brain of a baby fly have been mapped in full, creating the largest whole-brain 鈥渃onnectome鈥� described to date. It should allow researchers to understand how signals travel through a fly鈥檚 brain, how different regions of the brain interact and ultimately how specific behaviours are generated at the neural level.
鈥淎ll neurons of the brain are reconstructed and all the connections have been analysed,鈥� says at the University of Exeter in the UK, who wasn鈥檛 involved in the research. He calls the work 鈥渧ery significant鈥�.
Brains are mostly made of cells called neurons, which have long branches linking them together. Neighbouring neurons can signal each other at junctions between the cells called synapses, where one neuron releases a chemical called a neurotransmitter and the other receives it. The complete map of the neurons in a brain and the synapses聽is called the connectome.
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Biologists have mapped the connectomes of a handful of relatively simple animals. The first was the nematode worm Caenorhabditis elegans, which has just 302 neurons in its entire body and was mapped in the 1980s. More recently, in 2020, .
Other groups are working on the connectomes of animals with larger brains, like mice and humans. However, because the data sets are vast, reconstructing these connectomes is a challenge.
The new connectome, mapped by at the University of Cambridge and her colleagues, is that of the larva of a fruit fly, Drosophila melanogaster, a standard laboratory animal whose biology is known in detail. Zlatic declined to be interviewed about the work.
The team took the brain of a 6-hour-old D. melanogaster larva, cut it into 4841 slices and scanned them using a high-resolution electron microscope. The researchers then digitised the images and painstakingly reassembled them into a three-dimensional map. They studied the images with the aid of computer analysis until they could track neurons from slice to slice and identify all the synapses. The resulting map includes 3013 neurons and 544,000 synapses.
鈥淲hat is amazing here is just the sense of completion,鈥� says at Harvard University. The data reveals the 鈥渄eep logic鈥� of the neurons鈥� connections, she says.
Just mapping synapses doesn鈥檛 give you the full picture though, says at the Albert Einstein College of Medicine in New York, who in 2019 produced . Neurons can also talk to each other through slow-release chemicals like hormones and other connections between the cells, called gap junctions. All of these must be taken into account, he says, and he included gap junctions in his C. elegans connectomes, but the new connectome only has synapses.
In total, Zlatic鈥檚 team identified 90 types of neuron, each with a distinctive shape, pattern of connections and proposed functions, and also described the extent of the connections across the whole brain. Most sensory information coming into the fly鈥檚 brain propagates very quickly, says Dulac, taking just three hops from brain cell to brain cell to reach output neurons that help control the rest of the body. Furthermore, 62 per cent of neurons received information from every one of the larva鈥檚 senses. While the details are different, these overall patterns are similar to those found in other connectomes like that of C. elegans.
In a separate study, at Baylor College of Medicine in Houston, Texas, and his colleagues have developed a computational method to identify groups of interconnected neurons. They applied it to an existing connectome of about two-thirds of the brain of an adult D. melanogaster. Some of the groups of interconnected neurons contained thousands of brain cells and comprised smaller groups of cells nested inside each other.
The next big milestone is to map the brain of a mammal: first a mouse and ultimately a human. Given the rate at which computer technology is advancing, some researchers think the former will be possible within the next decade.
The human brain is an even bigger challenge, as it requires a data set 1000 times larger than the already enormous one required for the mouse. It also isn鈥檛 clear what we could learn from our connectome without first understanding simpler brains like that of the D. melanogaster larva in detail. However, in the long run a human connectome could help us understand our minds and behaviours, including the biological roots of mental illness.
鈥淲e鈥檙e dealing with such big questions,鈥� says Kunin. 鈥淲hat causes neurodegenerative disease? What causes us to think? They鈥檙e such big, complicated questions that being able to see a whole brain at the same time, I feel like it has to be part of the answer.鈥�
搁别蹿别谤别苍肠别:听bioRxiv, and
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