UQ research reveals how much we can learn about human consciousness by looking inside the brain of a fly.
You could be forgiven for thinking the humble fruit fly is a brainless drone, programmed only to fly around your kitchen in search of the bin.
However, UQ research is revealing there are more similarities between our minds and those of fruit flies than you might have imagined.
The work of Associate Professor Bruno van Swinderen from UQ’s Queensland Brain Institute (QBI) has been key in bringing this to the world’s attention – from showing flies have sleep stages similar to ours, to evidence they could even have a form of self-awareness.
Most recently, his research examining the brains of flies has revolutionised our understanding of how general anaesthetics affect human consciousness.
By revealing that, contrary to popular belief, general anaesthetics do more than just ‘put us to sleep’, his research has finally provided some clues about how these powerful drugs really work – potentially leading to safer and more effective drugs in the future.
General anaesthetic drugs have been used to sedate patients during surgery since the 1840s. Today, they remain one of the most frequently administered drugs in the world, with around 350 million administered worldwide each year.
Despite this, surprisingly little is known about how they actually work.
This mystery caught Dr van Swinderen’s attention when he began his PhD researching anaesthesia at Washington University, in St. Louis, Missouri (USA).
“I was studying general anaesthetics themselves, but I realised I was much more interested in what got lost when you used them – which is our consciousness,” he said.
Initially working with worms, Dr van Swinderen wondered whether they lost consciousness like us when subjected to general anaesthetics. More importantly, he wondered whether they even had any consciousness to lose in the first place.
While scientists and philosophers have been debating for centuries about what constitutes ‘consciousness’, most agree an entity is ‘conscious’ if it has a subjective awareness of things going on inside and outside itself.
So, one of Dr van Swinderen’s first tasks was to find out whether he could find evidence of this ability in insects – choosing fruit flies because of their simple and well-documented nervous systems.
Are flies aware of the world around them?
As you might imagine, there aren’t any off-the-shelf devices for testing fly consciousness. So, Dr van Swinderen had to get creative.
“I placed flies inside a virtual reality world and monitored the electrical activity in their brains,” he explained.
“I was surprised to find they were focusing their attention on one virtual object at a time. Their brain activity also waxed and waned depending on whether objects were startling, and disappeared when they fell asleep.
“This showed me flies could pay attention to the outside world, so I next wanted to know how aware they were of their own internal world.”
To answer this question, Dr van Swinderen’s team came up with a virtual reality game made just for flies, which they called the ‘Dodecahedron’.
When a tethered fly walks around inside the Dodecahedron’s virtual reality environment, their movement causes objects on the display to move around in a matching way. They exploited this to test the flies’ sense of control.
“We found that when a fly is in control of its visual environment, neurons across its brain started firing in a highly synchronised pattern,” Dr van Swinderen said.
“When the flies weren’t in control of the virtual environment, because we were just showing them a movie of their past actions, the brain cells were firing in a less synchronised way – even though the movies they were seeing were identical.”
The switch in brain states between conditions showed the flies could indeed be aware of the consequences of their actions. While rudimentary, this simple self-awareness could represent the basic roots of our more complex human consciousness.
Having shown flies pay attention to the world like humans do, Dr van Swinderen had other questions about how flies might be like us. One in particular he set out to answer: do flies dream when they’re asleep?
Image: David Spears FRPS FRMS/Clouds Hill Imaging Ltd./Getty Images
Do flies dream at night?
Around the turn of the last century, it was discovered that flies have a period of several hours (between eight and 12) a day when they are inactive.
What wasn’t known was what this inactivity truly meant. Was it sleep in the way we know it?
When humans sleep, our brain activity changes. We cycle back and forth through phases of deep sleep and a ‘wake-like’ sleep (where the brain is highly active and dreaming, also known as ‘REM sleep’).
Dr van Swinderen wanted to know whether flies also have sleep stages. But studying sleep in flies presented another interesting set of challenges.
Unlike humans, you can’t watch for the droop of an eyelid – flies don’t have eyelids. You can’t wait until they curl up somewhere to know they are asleep – flies don’t have a typical sleeping posture. If a fly is standing around not moving, it could be asleep, or quietly awake contemplating the universe.
So, how can we know that a fly is asleep?
Dr van Swinderen’s solution was the DART machine.
Specially designed by his team, the Drosophila ARousal Tracking (DART) system uses cameras and small motors to track the movement of several individual flies, each contained in its own glass tube.
What was new about the DART machine was that it could provide precisely controlled and timed mechanical ‘bumps’ to the flies in their tubes. If a fly had been inactive for a while, the machine could bump its enclosure and see what it did. If the fly responded to a light bump, it was probably in a lighter stage of sleep. If it stayed immobile even after a big bump, it may be in a deeper sleep stage. If it was just quietly awake, it would respond to every bump.
By tactically ruining the sleep of thousands of flies, Dr van Swinderen was able to make his next big discovery.
“We found flies that were still for 15–20 minutes were harder to wake up than flies that had been immobile for five minutes,” Dr van Swinderen said.
“But if you wait a little longer, the flies might become more responsive again – even though they still haven’t moved at all.
“The explanation for this is that the brain is cycling in and out of sleep stages, which we have now confirmed by recording from their brain while they sleep.”
“This is fascinating because it tells us that, even though flies have a tiny little brain, it is doing the same thing the human brain does.”
Flies were looking more and more like us with every discovery.
How do general anaesthetics really work?
After starting his journey looking at general anaesthetics 25 years ago, Dr van Swinderen has circled back to this topic and used his findings about how flies’ brains work to answer a long-held question about the relationship between anaesthetics and sleep.
“The current theory is that general anaesthetics activate sleep pathways in your brain. You pass out like during deep sleep, and surgery can proceed,” he explained.
“The whole idea didn’t make complete sense, because we knew general anaesthesia had to be more than just sleep, because people are putting knives into you and you don’t wake up.
“We also knew, however, there must be some correspondence between anaesthesia and sleep, because animals that have a propensity to sleep are more sensitive to general anaesthetics.”
In 2018, Dr van Swinderen’s work made headlines when his team was able to show that – as he had suspected – there was more to general anaesthesia than just ‘putting you to sleep’.
“It seems that the first step in general anaesthesia, especially at low concentrations, is indeed to put the brain to sleep by exploiting the brain’s natural sleep pathways,” he said.
However, especially at the higher concentrations that are required for surgery, he and his team noticed a second, previously undocumented, effect.
“The anaesthetics caused a disruption in the way neurons in the brain communicate. Specifically, the machinery needed for brain cells to communicate by releasing chemicals became gummed up in a sort of traffic jam.”
His work suggests the first effect of general anaesthesia is probably restricted to the sleep circuits of the brain, but the second effect may be much more extensive.
“The fly brain has millions of points of communication among neurons, known as ‘synapses’,” Dr van Swinderen said.
“The human brain has trillions. If all of those points are being gummed up, then you can see how the brain wouldn’t work anymore, and become totally unresponsive.”
As a kind of metaphor, this impairment in communication between neurons is something like getting hit on the head.
“If you have a concussion, the reason you are knocked out is because you have lost coordination between cells in your brain. It takes time to re-establish that,” he said.
“It’s amazing the brain can even recover from that. It has to go back and reassemble itself from where it was.”
Image: shapecharge/Getty Images
Can we make anaesthetics even safer?
Dr van Swinderen does not wish people to be alarmed by this finding, emphatically supporting that today’s anaesthetics are safe. His findings could explain, however, why the anaesthetics of 100 years ago were much less so.
“The hypothesis we’re working on is that the safe anaesthetics we use today put you to sleep nicely first, as a courtesy in a way, then they ‘hit you on the head’ to allow surgery to proceed,” he said.
“In contrast, it could be that the dangerous anaesthetics of old, like chloroform, just ‘hit you on the head’. A significant number of people didn’t recover from chloroform.”
His findings are being welcomed by those in the medical community, and he was invited to share his findings at the 2018 International Society for Intravenous Anaesthesia in Malaysia.
“I think many of the anaesthetists were interested to find out what the drugs they were administering actually do,” he says.
“We’ve been using general anaesthetics for almost 200 years, but we still didn’t really know.”
Dr van Swinderen’s team is now working to better understand which general anaesthetics cause more of a sleep effect and which cause more of the (potentially riskier) neural communication effect.
Alongside reducing side effects like nausea or recovery complications, this change could make general anaesthetics even safer for people whose neural communication is vulnerable – like children whose connections are still growing, or those with dementia who are losing connections.
“If we could dial these two effects – sleep and neural communication – up or down separately, that could be a real game changer.”
Learn more about how flies sleep like babies and the similarities between sleep and general anaesthesia in these podcasts with Dr van Swinderen, produced by the Queensland Brain Institute.