I Smell Trouble

by BotsAndBrainz

Hello again! Life has been nothing short of a mad rush, with a final presentation for my current project at work to be put together and given – and now a manuscript to put together for (hopefully soon) submission to a random journal! But before the craziness of the academic version of door-to-door evangelism begins anew (Dear Editor, would you have time today to talk about MY NEWEST GROUNDBREAKING THEORY?!) , I am making the most of my downtime to go on with the story I started in my “Love letter to the fruit fly brain”.

Memory and learning is not just useful to keep track of the numerous hobbies we all have. It has affected our existence on this planet unlike any other behavioral trait we display. If not for the stories told for us to believe in; to share our morals, values and beliefs through those stories with each other; to remembering and retelling tales -without our enormous capacities to memorize and learn, we wouldn’t be here. Think about it. Humans as a species are pretty darn mediocre. We aren’t very fast runners. Heck, I get tired from walking up six flights of stairs, leaving me to envy migratory animals, which can cover hundreds of kilometers in a single day. We can’t smell very well. Don’t ever get your hopes up that one day you’ll be able to smell where your friend has disappeared off to in a bar, a week after your last visit together. A properly trained bloodhound would have no issue with that whatsoever.

What we are better in than a bloodhound is memorizing. Admittedly, sometimes we don’t even do that very well (I’m looking at you, right-wingers all over Germany, forgetting the wall we tore down basically yesterday and now clamoring for a new one on our southern border). Despite this, we are singular in telling each other stories, memorizing them and learning (hopefully) from our past mistakes. The stories we tell each other are how we change the world. The brain stores all those memories, all the morals, all the values, everything we’ve been taught to believe in and brings them together to form the ever-shifting kaleidoscope of who we are as an individual. How does the brain do it?

That’s what I’m aiming to figure out using Drosophila Melanogaster. Fruit flies, as I’ve mentioned before, are pretty smart little critters, despite their brain size. With only 300.000 neurons at their bidding, they are truly “Keeping It Sweet and Simple”, and with that, are a pleasure to study. One day, the questions I’m asking will hopefully reveal how molecule interactions make learning and memory possible in this simple brain model. It sounds like a basic mapping job, with no application goal in mind. But what if we use this knowledge to help patients with learning disorders? One of the most well known disorders is PTSD – the Post Traumatic Stress Disorder. One of the main symptoms is overgeneralization. Can fruit flies really help us cure soldiers returning home from war of this terrifying illness? But first thing’s first: what is overgeneralization? Time to explain the ying and yang of learning, generalization and specificity.

Memories are linked to objects, contexts, sensations. For the Bot in the picture, the cookie has no connection yet. (I’ll get back to the cookie later, though.)

Lime Cookie Snatcher
Same works with cookies: You’re eating your boss’s cookies (which you shouldn’t be). The cookie is not connected with a memory…

For now, let’s use a streetlight as an exemplary object to which we connect memories. Imagine you’re a tourist waiting at a streetlight. One thing that (thankfully) never changes, no matter where you are on this beautiful planet, is that red = stop and green = go. You’re learned to ignore all the decorations or pictures or other differences between streetlights in different countries. In order to keep you safe when crossing the street, your brain is generalizing. Let’s assume that now you’re a hobby streetlight-photographer. Suddenly the differences between pictures or decorations on the streetlights of different countries matter very much to you. You’re specifying. These two features are at the core of our learning, necessary in pre-modern times when being able to tell the difference between the growl of a creature meant running away either from a large predatory animal or a tiny bird testing out its new mating call. If you were to generalize all the time, you might unnecessarily leave behind a food source or a safe cave. If you specify permanently, the predator with a fainter growl than you’ve heard before will be left to enjoy a lovely, human snack.

Being able to switch between generalization and specification is healthy. In PTSD patients, the trauma leads to overgeneralization. This makes it nearly impossible for them to live a happy, normal, traumatic episode-free life. In these people, the brain connects a stimulus with a punishment that’s not actually going to happen. Let’s go back to being tourists. Crossing the street, you turn into a dark back alley. Out of nowhere a person carrying a gun, dressed in black, of average height, jumps out and demands you hand over your camera. You’re alone, defenseless and scared. So you hand over everything with shaking hands. Next thing you know, the person shoves you out of the way, and you’re hit by the overpowering scent of a lime perfume.

Zapping the Thief
… The lime cookie and its smell is now linked to being zapped with a taser. Not a good memory association to make!

Other than that, you’re unhurt. After reporting the incident, you go on with your life, albeit wary of dark alleys. Later – sometimes days, sometimes, years later – you’re shopping for ingredients to make a key lime pie. Just as you reach out for the key ingredient (limes), their smell hits you and your heart begins to race. You can feel the pain of the spike in adrenaline levels and frantically search the store for the person from the back alley.

Evil Limes
Now the lime triggers the bad memory all the time, even completely out of context!

But there’s no one around you. The flashback of the negative event (punishment) has been triggered by the olfactory stimulus completely out of environmental context. This is your brain overgeneralizing. Unable to see that logically it HAS to smell of limes (seeing as you’re holding them), it goes and retrieves the memory of the back alley and tries to save you by sending signals to your legs to get pumpin’ via the sympathetic nervous system. It’s sympathetic by saving (a part of the autonomic NS, which regulates unconscious actions) to get you to run far, far away.

It is overgeneralization that I tried to induce in my poor, little, naïve fruit flies. Using the UAS-Gal4 system, I can delete specific areas or even cells in their brain, and study the effect this has on their ability to store specific memories. By giving them an odor to smell (limes) and zapping with electricity them (I’m sorry, but it IS a PTSD experiment), I train them to remember bad vs. good smells. If they’re still able to tell the difference between bad (lime) and a different smell (orange), their ability to form specific memory still works. On the other hand, no difference shows the fruit flies can only generalize.

Does generalization in fruit flies mean they’re traumatized? Unlikely. Many of the symptoms of PTSD are very hard to produce in these tiny invertebrates. Fear incubation for example, is a key symptom, in which the trauma gets worse over time. My fruit flies tend to forget over time. Great for them, but bad for me trying to develop a model for PTSD. Despite not reaching my goal, the project did teach me how different factors can influence generalization and specificity. (And it’s always helpful to know how to learn more details for a test.) It most certainly did not traumatize me enough to steer clear of high-risk projects. And with that – on to new discoveries!

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