14/ And for all the Utahns: Alex will defend his PhD next week. 🎉

Join us!!

Come for the neuro-democracy,
stay for the olfactory homunculus,
and never underestimate the power of an outlier. 💗

13/ This work was led by the one and only Alexander MacKenzie with the brilliant and formidable @synapshotneuro.bsky.social and @jilianulibarri.bsky.social as well as many other teammates.

🤓 TL;DR

12/ The fly mushroom body encodes an olfactory homunculus: fruit odors get the hand and are easily learned, while toxic odors get the foot and are poorly learned.

Neuro-democracy: where every connection counts.

Read all about it here: www.biorxiv.org/content/10.1...

11/ We cannot say for sure, but VL1 projection neurons likely gate plasticity through inhibition, shouting at Kenyon cells, yet keeping learning locked.

(Maybe for the best: the VL1 projection neurons detect pyrrolidine, a real stinker. Better steer clear than to learn it as good! 😷)

10/ We biologists love a clean, simple rule, right?

But then came the VL1 projection neurons...

VL1 projection neurons break the rule — despite weak connectivity, they drive large Kenyon cell responses yet fail to support learning.

Why, oh, WHY? 😫

#uglydatawreckingourbeautifultheoriesagain

9/ This connectivity–function relationship sets the stage for learning: odors that activate many Kenyon cells are easy to learn.

Those that barely activate a few?

Basically unlearnable. 🤡

8/ Likewise, odors that activate highly connected projection neurons, like fruit odors, drive broad Kenyon cell responses.

Odors that activate poorly connected projection neurons, like those made by toxic microbes, not so much.

🍇🍎 Fruit odors get the hand.

🦠👾 Toxic microbe odors get the foot.

7/ Structure matters.

Highly connected projection neurons broadcast their signal loud and clear, reaching and activating many Kenyon cells.

Weakly connected ones fade into the noise.

What the brain builds, the brain listens to.

6/ The wiring is mostly random — as predicted by theory — but some projection neurons connect far more often than chance.

As if the dice were loaded. 🎲🎲🎲

5/ When looking at the connections between projection neurons and Kenyon cells we found clear biases.

Some projection neurons connect up to fifteen times more often than others.

Some occupied expansive stretches of connectivity estate, while others were left with just a narrow strip.

4/ The mushroom body is built like an expansion layer: a small number of projection neurons feed into thousands of Kenyon cells.

Classic theories predict that wiring is random, giving every odor an equal shot at being learned. 💯

But ugly data got in the way of these beautiful theories... 🧌

3/ Why?

Learning centers like the mushroom body face an existential dilemma: they need enough coding capacity to represent as many stimuli as possible while still prioritizing cues that matter most for survival.

How does the mushroom body balance this tension between capacity and selectivity?

2/ The fly brain does not treat all odors equally... rather it plays favorites. 😲

Think of it as a sensory homunculus... but for smell:

🍇🍎 Fruit odors get the hand — prime neuron real estate.

🦠👾 Toxic microbe odors get the foot — pushed to the corner.

Not all smells get an equal vote...

🔥🔥🔥

Science moves forward when we chase big, weird questions — the ones that make you think: Wait, can that even work?

The payoff is not always immediate — or ever! — but curiosity-driven science can bring new ideas, deepen our understanding, and change what we know in the most fundamental way. 🧪🔬

We finish this manuscript with more questions than we started with... a good sign! 🤓

What are these capsids transporting? Which cells release them?? Where do they go???👾🧑‍🚀

So, stay tuned: even in the tiny fly brain, these mechanisms might reveal how similar processes operate in our own. 🧠✨

This whole project started with one of @jasonsynaptic.bsky.social's wild ideas, so wild I thought it was nuts. 🥜🤪 Arc forming viral capsids that can regulate learning and memory in mice. AND IN FLIES? We tried it. It worked!! 🙃

HUGE shoutout to @barefeetsven.bsky.social — the driving force behind this work — who somehow survived having two PIs (@jasonsynaptic.bsky.social and me).

Talk about being between a 🪨 and a hard place…!! 💪🧠