Washington:

Scientists announced on Thursday a milestone in neurobiological research with the mapping of the entire brain of an adult fruit fly, a feat that may provide insight into brains across the animal kingdom, including people.

The research detailed more than 50 million connections between more than 139,000 neurons – brain nerve cells – in the insect, a species whose scientific name is Drosophila melanogaster and is often used in neurobiological studies. The research sought to decipher how brains are wired and the signals underlying healthy brain functions. It also could pave the way for mapping the brains of other species.

“You might be asking why we should care about the brain of a fruit fly. My simple answer is that if we can truly understand how any brain functions, it’s bound to tell us something about all brains,” said Princeton University professor of neuroscience and computer science Sebastian Seung, one of the co-leaders of the work published in a series of studies in the journal Nature.

While some people may be more interested in swatting flies than studying them, some of the researchers found aesthetic satisfaction in peering at the fruit fly brain, less than 0.04 inches (1 mm) wide.

“It’s beautiful,” said University of Cambridge neuroscientist and research co-leader Gregory Jefferis.

The map devised by the researchers provided a wiring diagram, known as a connectome, for the brain of an adult fruit fly. Similar research previously was conducted with simpler organisms, such as the worm Caenorhabditis elegans and the fruit fly’s larval stage. The adult fruit fly presented more complicated behaviours to study through its brain wiring.

“One of the major questions we’re addressing is how the wiring in the brain, its neurons and connections, can give rise to animal behaviour,” said Princeton neuroscientist Mala Murthy, another of the co-leaders of the research.

“And flies are an important model system for neurosciences. Their brains solve many of the same problems we do… They’re capable of sophisticated behaviours like the execution of walking and flying, learning and memory behaviours, navigation, feeding and even social interactions, which is a behaviour that we studied in my lab at Princeton,” Murthy added.

One of the studies analyzed brain circuits underlying walking and discovered how flies halt. Another analyzed the fly’s taste network and grooming circuits behind behavior such as when it uses a leg to remove dirt from its antennae. Another looked at the visual system including how the fly’s eyes process motion and color information. Still, another one analyzed connectivity through the brain, discovering a large assemblage of “hub neurons” that may speed up information flow.

The researchers fashioned a map tracking the organization of the hemispheres and behavioural circuits inside the fly’s brain. They also identified the full set of cell classes in its brain, pinpointing different varieties of neurons and chemical connections – synapses – between these nerve cells, and looked at the types of chemicals secreted by the neurons.

The work was conducted by a large international collaboration of scientists known as the FlyWire Consortium.

(Except for the headline, this story has not been edited by NDTV staff and is published from a syndicated feed.)

Masato Tsuji has been observing insects since he was a child. He loves studying flies, so much so that he shows them horror movies and scares them – all to understand what happens in their brain when they’re afraid.

“Our discovery may provide a clue to treat psychiatric diseases stemming from exaggerated fear, such as phobia and anxiety disorders,” Dr. Tsuji, an assistant professor at the University of Tokyo, told this writer.

Do flies feel fear like we do?

It’s easy to question our understanding of a fly’s feelings. After all, the fly’s brain and evolutionary history differ from ours. Fear is also a humanised emotional state. So we can’t say for sure whether flies have feelings.

However, previous research has shown that flies exhibit defensive responses that resemble fear-like emotional states. The response leads to changes in the internal brain state. So flies offer an opportunity to study the neural and molecular basis of a fear-like state.

A horror movie for flies

To understand fear, researchers Dr. Tsuji, Yuto Nishizuka, and Kazuo Emoto built a virtual reality arena – a mini theatre for flies – fit with lights, cameras, screens, and a scary action scene.

What scares flies? A puff of air and a small black dot the size of a spider, their natural predator, moving around.

But first, the researchers had to get tiny fruit flies (Drosophila melanogaster) one by one into the mini theatre. It was a delicate task. First, Dr. Tsuji tethered a sedated fly to a small rod with a dribble of glue on its back. Once it woke up, it would find itself on a small Styrofoam ball suspended over a thin layer of air created using an air compressor. The fly could rest or walk around on the ball.

After the fly became acquainted with the setup, the movie began on an LED screen in front. While the dot moved on the screen, a small nozzle over the fly blew puffs of air.

Flies avert their gaze

As the dot moved after an air puff, the flies started to walk on the ball, turning away from the dot. All flies responded to the dot only when paired with an air puff as well.

Some flies froze or jumped, but most turned and ran away from the threat.

According to Dr. Tsuji and his team’s paper, published in the journal Nature Communications in July, a cluster of 20-30 neurons in the visual regions of the fly’s brain is responsible for this behaviour.

The fear neurochemical

Dr. Tsuji’s team took advantage of the variety of tools to genetically modify and study fruit flies to isolate a set of mutant flies. By manipulating and recording the activity of their neurons, they found that a neurochemical called tachykinin activated the flies’ aversion behaviour.

That is, flies that had a mutation that deprived them of neurons that could release tachykinin didn’t display the threat avoidance behaviour, even if they retained other visual and motor responses.

“This molecule causes anxiety-like symptoms in mice and humans,” Dr. Tsuji said. “At the level of molecules or genes, perhaps the fear-like mechanism is preserved across animal species.”

That could explain why we may look away from scary scenes in films or animals like snakes.

A neurochemical wave of fear?

Dr. Tsuji focused further on the finer details of the activity of tachykinin-releasing neurons. 

Normally, an influx of calcium ions coincides with the electrical activity of neurons. More calcium in the neurons indicates an active neuron; less calcium shows an inactive neuron.

So a microscopy technique called calcium imaging helped Dr. Tsuji’s team visualise how neural activity in fearful flies changes with time. 

To their surprise, they found that the activity of the tachykinin-releasing neurons increased and decreased rapidly, as the amount of calcium in their neurons went up and down like a wave.

Such oscillating neural activity is rare for Drosophila melanogaster, though the evidence has been accumulating as the technology has developed to record such small and fast neural activity fluctuations.

When the team artificially generated the wave-like calcium activity patterns in their neurons, flies turned away from the stimulus. “That wave signal, we believe, is functioning as a fear-like command that drives the escape behaviour,” Dr. Tsuji said.

An application

Neural activity oscillation occurs in the fly brain only during a fear-like emotional state. However, Dr. Tsuji speculated that in the brains of the people with phobias and anxiety, the wave-like neural activity pattern could occur even in response to a neutral stimulus.

He expressed hope that their work would cast light on why phobic patients overreact to usually non-frightening stimuli. “If I can be speculative, one possibility is that humans have similar neural circuitry that drives the escape behaviour in the brain.”

“If this possibility is true, perhaps we can intervene with such activity patterns in a targeted way to help alleviate the fearful symptoms,” Dr. Tsuji added.

Mapping the fear circuit

The neurons regulating the aversion behaviour are in the visual region of the fly’s brain, so the team wants to understand how they regulate vision. That is, how is visual information transmitted to elicit the fear response?

They are now working to reveal further details of fear and its effects on vision in flies. “We want to build a complete circuit diagram of how fear regulates vision,” Dr. Tsuji said.

His curiosity as a child observing insects in his garden might one day help discover the intricate workings of their little brains sensing fear, and potentially benefit many patients suffering from phobic disorders.

Ravindra Palavalli Nettimi is a project specialist at the Office of Research Strategy and Development at the University of Tokyo.