Thread by @giorgiogilestro

Nobody knows what the function of sleep is, but we know that it cannot be achieved without disconnecting us from the external world. Sleep is not compatible with a fully conscious experience. Why? We investigate this in our latest paper on @nature 🧵1/25

rdcu.be/cyE9t

In any animal, a fully conscious state and sleep are not compatible, to the point that one of the definitions of consciousness is that “all that is lost while we are in dreamless sleep”. 2/

The fact that the brain has to surrender to the tyranny of sleep is also the main reason why scientists believe (in a rather dogmatic fashion) that sleep is “of the brain, by the brain for the brain“. 3/ nature.com/articles/natur…

Yet, even during sleep parts of our brains retain some ability to process external information. In 1960, Oswald et al formally showed that sleeping humans could wake up in response to some salient stimuli, such as their names being called ... 4/

... but not in response to stimuli of identical strength but no salience, such as other people’s names or their names played in reverse! 5/

This finding has been confirmed and extended over the decades in the scientific literature, providing evidence that it applies to even more complex nuances of saliency, such as an angry tone of voice. 6/

But, as it often happens, the scientific literature is certainly less comprehensive and (less amusing) than the phenomenon in its entirety. 7/

And not just in animals. The human brain is certainly able to perform some very puzzling decoding during sleep. 8/ tiktok.com/@sophie_grace_…

Even though we have scientific evidence that animals can wake up to salient sensory stimuli during sleep, hardly anything is known about the underpinning biology. Enter: Drosophila melanogaster! What better animal model than flies to dissect this amazing brain property? 9/

Postdoc Alice French @AliceisnotFren1 took the lead on this amazing project to show that even flies can recognise salient stimuli in their sleep and react accordingly, modulating their response based on their internal state. 10/

We initially expanded this amazing robotic platform we had previously built in the lab, called #ethoscopes, which allows us to monitor and interfere with flies using inexpensive @Raspberry_Pi computers. We can work with 2000 flies at once and have the PIs control their sleep 11/

Alice wanted to build a robotic component able to challenge single flies with specific odour but only while they were asleep, to record whether they would wake up or not. She obviously started with LEGO ! 12/ @LEGO_Group

In our first prototype, we built a robot able to operate a LEGO valve so to send a puff of air to the sleeping fly. LEGO valves were a good start because we needed 500 of them... 13/

The system worked and we went from this early prototype ... 14/

to the final product 15/

Using this ethoscope module we could challenge sleeping flies with different odours and check whether they would respond differently to some of them. We found they did! Flies would respond to 5% acetic acid for instance but not to 10% acetic acid 16/

Not only that, the valence of the odour could be modulated by internal states. Flies that had received a little starvation were increasing their response specifically to food-related odours 17/

When we gave alcohol to flies, on the other hand, we found drunk Drosophilae were less responsive to odours in general showing somehow a deeper sleep state. 18/

Now, flies are arguably the best animal model to study circuit neuroscience these days. We have a full connectome of the fly brain and countless genetic tools that allow us to turn neurons on and off 19/ arstechnica.com/science/2020/0…

So that is what we did. We started turning neurons on and off in the fly brain, looking for some that would modulate their ability to sense stimuli during sleep. We found them! 20/

We actually found the whole circuit, connecting the "fly nose" all the way to the sleep centers in the brain. 21/

And when we used thermogenetics to switch those neurons on or off with infrared radiation, we could interfere with that process and make the flies more or less responsive. 22/

What have we learned? 1) That even sleeping flies, like mammals, can discriminate sensory stimuli in their quality during sleep. 2) We identified the circuit that does so in the brain, suggesting that some neurons in our brain are "awake sentinels" while the others "sleep"! 23/

And 3) we showed that flies can be used to successfully investigate very complex problems, like subconscious processing of information. If you want to know more, @AliceisnotFren1 and I discuss these findings in this video abstract. 24/

While here you can read the news and views written by Wahne Li and @AlexCarlKeene. Together with @AliceisnotFren1 the other amazing authors of this super cool story are @qgeissmann and @BeckwithEsteban
nature.com/articles/d4158…