They complete the first map of an insect’s brain and its neural connections

Famous Spanish Nobel Laureate Santiago Ramón y Cajal is credited with the following quote: “As long as the brain is a mystery, the universe will remain a mystery.” Understanding human consciousness is one of the greatest scientific challenges in history, comparable to puzzling questions about the cosmos like what dark matter really is or how gravity and quantum combine.

Now, a team of researchers has gone a step further to understand the complexity of the human brain, using a typical model in genetic studies: the brain of larvae of the fly Drosophila melanogaster, or simply the fruit fly. The scientific article reproduces to date the most advanced map of the connections of a brain that we have, including 3,016 neurons and each of the 548,000 connections between them.

The authors, who are from Johns Hopkins University (USA) and Cambridge University (UK), aim not only to lay the groundwork for future research on the human brain, but also to inspire new architectures for machine learning, the computer procedure in which artificial intelligence (AI) is based.

If we want to understand who we are and how we think, we first have to understand the mechanism of thought. And the key is knowing how neurons connect to each other.

Joshua T. Volgelstein, Johns Hopkin University

But mostly, the study tries to fit one more piece into understanding our consciousness, as lead researcher Joshua T. Volgelstein of Johns Hopkins University explains: “If we want to understand who we are and how we think, we first have to understand the mechanism of thinking. And the key to that is to know how the neurons are connected to each other”, he explains.

High resolution images of the brain

The Cambridge neuroscientists created the high-resolution images of the brain and manually studied them to find individual neurons, rigorously tracking each one and linking its synaptic connections. The team turned the data over to researchers at Johns Hopkins, who spent several years using the original code they created to analyze brain connectivity.

The Johns Hopkins group developed techniques for finding clusters of neurons based on shared connectivity patterns and then looked at how information might propagate through the brain.

The authors found that the most active circuits in these larvae’s brains were those running to and from neurons in the learning center.

Finally, the entire team recorded each neuron and each connection, classifying each neuron according to the role it plays in the brain. Thus, they discovered that the most active circuits in the brain of these larvae were those that went to and from the neurons of the learning center.

Half a century of trying to create a map of the brain’s connections, or connectome, ended in this revolutionary result, published today in the journal Science.

A study started in the 1970s attempted to map the brain of a nematode worm. The result was a map and its first draft was published in 1986 by the Nobel Prize in Medicine Sydney Brenner, who died in 2019.

Partial connectomes have been mapped in many systems, including flies, mice and even humans, but these reconstructions typically only represent a small fraction of the total brain. In fact, integral connectomes have only been generated for several small species with a few hundred to a few thousand neurons in their bodies, such as nematodes or marine annelids.

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Diagram of the fruit fly larva connectome. / U. Johns Hopkins / U. Cambridge

A useful model also in neuroscience

But why use Drosophila melanogaster or fruit fly and not another animal more like human being? This species has been common in genetics laboratories for decades. The reasons are diverse and are due, in part, to the functionality provided by working with this insect, but also to the fact that it has characteristics similar to those of mammals.

To map the brain of the fruit fly larva took about a day per neuron. A rat’s brain is about a million times bigger.

As for their brains, they are the size of the head of a pin. However, fruit flies reproduce many behaviors rich in learning and decision-making, making them a useful model organism in neuroscience as well as genetics.

Another advantage is that the image of the brain of the Drosophila fly and the reproduction of its connections were possible in ‘only’ 12 years. This, according to the researchers themselves, is “a reasonable time frame”.

Will the human brain ever be mapped?

Mapping entire brains is difficult and time-consuming, even with the latest and greatest technology. Obtaining a complete cellular-level picture of a brain requires “cutting the brain into hundreds or thousands of individual tissue samples, all of which must be captured with electron microscopes before the painstaking process of reconstructing all these pieces, neuron by neuron, into a complete picture”, details the study.

To map the fruit larvae’s brain, it took about a day per neuron. As a mouse brain is about a million times larger, the possibility of mapping anything that looks like a human brain is virtually unattainable.

“It is not likely that we will be able to map the entire human brain in the near future; we may never make it,” the authors acknowledge.

Open source to be used by other researchers

The work of fruit fly larvae revealed features of circuitry in their brains that powerfully resembled machine learning architectures. Thus, the team hopes that the continued study of these patterns will reveal even more computational principles, perhaps inspiring new artificial intelligence systems.

On the other hand, the methods developed by Johns Hopkins University are applicable to any brain-wiring project, and their code is available to anyone trying to map an even larger animal brain, say the authors. Volgelstein himself, the principal investigator, hopes that other scientists will be able to face the challenge of trying to map, this time, the mouse brain. “Maybe in the next decade,” he estimates.

While the study by Volgelstein and colleagues managed to map the brain of the fruit fly larva, other teams are working to achieve the same result, this time in the brain of the adult fly. When that happens, the next step would be to make comparisons between the connections in the adult and larval brains, as recognized by one of the study’s authors, Benjamin Pedigo.

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