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Lord of the Flies-Optogenetic Fruit Fly Conditioning

You know what’s great about fruit flies? Nothing.













fig. 1 Fruit flies suck

Nothing, that is, other than their benefit as a model organism for simple and fast transgenic experimentation — but who really cares about all that. Drosophila melanogaster are butts, so what if they could die? Well they can (vinegar and plastic-wrap), we don’t need science for that. We can go one further. What if we can make the flies loathe existence as much as the rest of all life hates them? What if we could take away the one thing that makes their nasty, brutish, and short existence bearable?  Make them lose life’s purest love? The love of…sugar?


Yeah, we did that.





Look at this little guy, basking in the sweet, sweet 625nm rays of ghost sugar:
















fig. 2 How long can you hold out against science little guy, how long?

If you remember from my first post, red light activates the Gr5a sweet taste neuron, making the fly feel like a kid in a candy store after the adult-apocalypse. Now if we interrupt this tiny love affair with a SYRINGE OF SCIENCE and also quinine we can get the fly to associate the bliss of sugar (which flies love), with the bitter sting of quinine (which flies do not love).

Syringes-delivering Science since 1st century CE

Syringes-delivering Science since 1st century CE
















That’s classical conditioning, Kyle. After a few pairings of the two, the flies become depressed. Or I would, if I were a fly, because at that point they can’t stomach anything sweet, and don’t even respond to a fly sized glob of syrup. I’d do things to a human sized glob of syrup you’d probably try to get me arrested for, and the knowledge that science could some day deprive me of this pleasure is a sobering thought. After this I sat in a dark room for 3 days eating candy.

When I came out, the data was still there and I learned to love the bomb. Here’s a bit more detail on the way we played with fly tastes and the numbers we got:













fig. 3 What I done do to them flies

The flies were taken off of food for 12hr before experimentation, then adhered to a foil slide with nail polish and mounted on a stand. For the conditioning test (A, purple), proboscis extension reflex (PER) was first tested via optogenetic, and then actual sugar stimulation, to establish a baseline of both the light-induced and real sugar-induced response.  For each trial, PER was optogenetically induced 3 times, and quinine applied to the extended proboscis. After 3 trials, PER was measured as a response to light, and then sugar again. A simple control used non-optogenetic flies-with the gene for the optogenetic channel, but no second gene activating its expression, and then the same opto/quinine pair trial (B, purple).  For further control trials, (C, red) quinine was applied to the proboscis sans opto- stimulation, (D, yellow) opto- stimulation was paired with water, and (E, green) opto- stimulation was used without quinine.  Though this may seem like a lot of controls experiments, we want to establish as firmly as possible that the response we are getting is solely a result of the paired conditioning experiment we are running.














































These data show strong aversion to sugar after the conditioning. Only the trials where sweet taste activation is paired with bitter shows a marked decrease in response to sugar over the average indicating that the result was due to conditioning, not random chance. Future experimentation will also see pairing the light activation with a neutral taste to the flies, like salt, to see if we can condition the flies to respond to salt as they respond to sugar, as well as the possibility of optogenetically activated bitter taste activation combined with the introduction of real sugar. Optogenetics is the cutting edge of neuroscience technology, however, so whatever comes next will be exciting!

Mind Control. With Lasers.

Coming soon to a backyard near you.

At least, that’s the idea. We’re sure the technology will catch up if we give it enough prodding and throw an intern or two its way. And hey if not? There’s still lasers, sounds like a win/win to me. Wait we don’t get lasers either? This is really going downhill fast. Apparently the higher ups don’t think beams of focused high energy photons wantonly sprayed at the brains of schoolchildren is good science.


I don’t see why anyone would have a problem with this

Ok you know what, how about beams of somewhat lower energy photons, and brains of something whose parents won’t send us more angry letters after little Johnny tattletale has another run in with the burn ward. How about LEDs and a bug? Well then.

Mind control.

Coming soon to a backyard near you.

And it is. Technically. So long as the mind you want to control is our tough lil buddy Drosophila Melanogaster AKA the fruit fly. And so long as the nefarious deeds you want your insatiable army of insect minions to thoughtlessly carry out is…sticking out their tongue. THEN YES. We’ve got mind control.


It’s called optogenetics, and it’s pretty crazy stuff, really. Long story short, we can stick a gene into the fruit flies that makes certain neurons, say, the sweet taste receptor Gr5a, sensitive to certain wavelengths of light-in this case, red light, because it is capable of passing through their exoskeleton into the neurons beneath. That way, if you set the little guys in front of an LED and blast away, they think the Kool Aid man just suplexed their face. And what is a fruit fly’s reaction to opening the floodgates of sugary heaven? They stick out their tongue.

It turns out you can rig up an LED with a microcontroller so that when two wires from the circuit come in contact with the fly, it completes the circuit, treating the fly as a resistor, and activates the LED. This lets us time contact with the fly to when the fly receives light (and therefore sweet-tasting) stimulation.

If that was a little hard to see, here’s an up close and personal version of the events.

And of course, nothing is truly scientific until we’ve mechanized it

It might sound trivial, but there’s actually a lot to getting a response like this without any invasive action other than light stimulation. Optogenetics really opens a lot of possibilites up for experimentation that just weren’t feasible before. It took the world of neuroscience by storm just a few years ago and is on the short list for the Nobel Prize, and we‘ve got a crack team of top scientists working to bring this technology to your own backyard.

Ok, slight exaggeration again, maybe, they’re actually interns working on it. Well, an intern. But we’ve stuck him in our basement with a steady supply of mountain dew and cheetos, and if that’s not science, I don’t know what is.



I’ve just been told that in fact its not actually science. According to them, “good science” involves some sort of method, and numbers, and repeatable experimentation. Apparently blood, sweat and cheeto dust just aren’t enough for some people. We’ll have the intern fill you in on the details.

Cort continues his Optogenetics Odyssey in this week’s installment of “Pretty Fly for a White Guy”

Hello, again. I’m Cort, the fly guy (I also do research with fruit flies) at Backyard Brains.

Since the last time I posted I’ve made significant progress in my research! IT WORKS!!!

In the above video what you’re seeing is one of the flies I’ve bred having its proboscis extension activated with an LED. Optogenetics works! Now that I have it work, I’ve been busy playing with the new “flyscope” and raising more transgenic (organism with dna put into it from another organism, in this case the light sensitive protein) flies for my experiments. In order to breed the flies that I need, I had to dive straight into a world of genetics and Fly husbandry. I spent quite a bit of time at the University of Michigan Shafer lab learning about Drosophila (fruit flies) and how to raise them.


Fly husbandry is pretty intimidating at a glance, but once you break past the complexity it really isn’t so bad. It’s common knowledge that most complex organisms undergo a process called “recombination” during meiosis (when sex cells or “gametes” are formed in the body). One of the main reasons that scientists love using fruit flies to conduct genetic experiments is (more…)