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A major advance in mapping the structure of the brain

TechScienceA major advance in mapping the structure of the brain
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Teathat cognitive The abilities of a fruit fly-larva may not seem particularly remarkable. This creature—the early, worm-like stage of a fly—is only able to sense its environment, search for food, and avoid predators. Its brain does not yet know how to walk, fly or even see properly. And yet its limited capacity is still, in miniature, a useful model for larger and more complex brains.

This week, researchers published the first complete map of the brain of such a larva. This “connectome”—the equivalent of a three-dimensional circuit diagram—charts a brain’s neurons as well as the locations of synapses, the junctions where brain cells pass information between each other. The structure of these circuits affects the types of computations the brain can perform. Knowing how neurons are interconnected could give scientists a more mechanistic understanding of how the brain works.

Until now, the production of connectomes has been limited to simple organisms such as nematode worms, which have hundreds of neurons in their brains and in which complex behavior has not yet been observed. Or smaller parts of the larger brain – including that of the fruit fly – have been mapped. However, never before had the entire brain of such a complex organism—the approximately 548,000 connections between 3,016 neurons in the case of a fruit-fly larva—been mapped.

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Latest work, published in Sciencemarks the culmination of a more than a decade-long effort launched at the Genelia Research Campus in Virginia as part of its flyem Project. The first step involved dissecting the tiny larval brain into thousands of layers to scan with an electron microscope em of name). The researchers then painstakingly labeled and analyzed the images, mapping out regions associated with functions such as vision, for example, or olfaction.

The connectome of fruit-fly larvae has already provided insight. For example, areas of the creature’s brain associated with learning had more loops in their circuitry, with downstream neurons connecting to those behind them than other areas of the brain. This suggested some repetitive processing of signals. One proposed explanation is that such loops encode predictions, and organisms learn by comparing these with actual experiences.

Information about the taste of a leaf, for example, may enter a neuron along with a prediction based on previous meals. If the taste varies from predicted, the neuron can secrete dopamine, a chemical capable of rewiring the circuitry to form a new memory.

Biologists have much to learn from combinators. Marta Zlatik, a neuroscientist at the University of Cambridge and author of the latest research, envisages a combinatorial study program with three phases. First, a connectome map is performed. Second, the pattern of activity in a living brain is imaged when an animal performs a task. And third, this information is combined to pinpoint differences in brain structure worthy of laboratory manipulation or reproduction in order to test hypotheses experimentally between individuals with different brain structures.

To understand the origins of intentionality, for example, or how a fly decides to perform an activity such as moving forward, a person’s brain would be scanned while it moved. Then, regions showing activity will be analyzed in conjunction. Other flies can silence those specific brain circuits and, by comparing the behaviors of different individuals, scientists will be able to pinpoint the role played by specific brain regions in how a fly performs an activity. “The future,” says Dr. Zlatik, “is comparative connectivity.”

It seems achievable now. even in the decade since the flyem project began, technology has advanced dramatically. involved in nanoscale salami-slicing em Can now be done in weeks instead of years. Analysis can also be speeded up: Now that the laborious task of labeling larval connectives has already been done by hand, a machine can be taught to do it again on a different individual’s brain.

Dozens of groups are moving forward. another branch of the flyem The team is dealing with the adult fruit-fly connectome, which has ten times as many neurons and a much larger visual cortex. Other groups are encountering the zebrafish, a relatively facile vertebrate. However, the biggest game in the crosshairs at the moment is the mouse. With a brain volume a thousand times larger than that of a fruit fly, researchers are currently moving forward one cubic millimeter at a time. Still, says Moritz Helmstedter at the Max Planck Institute for Brain Research in Frankfurt, who leads one such project, a full mouse connectome is quite achievable, if several hundred million dollars away.

Of course, the ultimate prize is the human brain, which is still a thousand times larger and vastly more complex. But when, if ever, that full combinatorial treatment can be given remains to be seen.

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