Thread by @zhaozhilei

Ever wonder why some mosquitoes like biting you more than the animals nearby? What’s unique about human odor and how can mosquitoes tell the difference? By opening their heads and reading their minds, we now have some answers. disq.us/t/3sn6fy5

Super excited to share our latest work by a dream team! @lindymcbr @JessicaLZung @AzwadIqbal @meg_younger @BenMatthewsUBC @UMDITF Alexis Kriete, Dorit Merhof, Stephan Thiberge and Martin Strauch

We studied the mosquito Aedes aegypti. It recently evolved to specialize in biting humans and thus became a major disease vector.

Females really LOVE human odor and can easily distinguish it from animal odor. But how exactly they tell the two apart remains unclear - especially at the neural level.

To investigate, we decided to record neural activity in the brain of females while exposing them to natural human and animal odor extracts.

We knew this would be hard - but it was harder than expected. We spent 4 years developing the necessary genetic reagents, odor delivery systems, and analytical approaches.

When we were finally ready to go, we were surprised by what we saw... which was not much!

Despite the complexity of human odor, which contains tens to hundreds of compounds, the neural response in a brain region called the antennal lobe was remarkably sparse.

Two glomeruli showed the most activity. One was equally sensitive to animal odors and other natural odor extracts (‘universal’). The other was more sensitive to human odor than anything else (‘human-sensitive).

The relative activation of just these 2 glomeruli was enough to reliably separate humans and animals across concentrations and across individual human/animal species variation.

What is it about human odor that generated this unique neural ‘code’? Vertebrate odors have a lot of simple, straight-chain aldehydes in them, and it’s long been known that human odor has a lot of decanal in particular (10 carbons).

Turns out this is unusual. Non-human animals give off more short-chain aldehydes, like hexanal and heptanal.

A deep dive into the literature by @JessicaLZung (who led the odor analysis) revealed that this difference almost certainly stems from the presence of a unique molecule in human sebum. It’s aptly named sapienic acid, has antibacterial properties, and oxidizes into decanal.

But back to the mosquitoes… The human-sensitive glomerulus was narrowly tuned to long-chain aldehydes!

On the other hand, the universal glomerulus is tuned quite broadly to many host compounds and we think it may signal the total odor concentration.

We propose a simple model of human odor coding: a comparison of activity in the human-sensitive (H) and universal (U) glomeruli provides a robust read-out of the relative concentration of long-chain aldehydes in a complex odor blend – and thus distinguishes humans from animals.

These signals can’t explain everything about host odor responses in Ae. aegypti. But we think they’re likely to be a dominant driver of the species’ strong preference for humans.

In fact, aldehydes play an important role in host attraction in lots of different mosquitoes. Could a ‘retuning’ of ancestral aldehyde-sensitive neurons to long-chain compounds partly underlie the evolution of human preference in Aedes…? Stay tuned for the next chapter!

And if you don’t care too much about mosquitoes, but like to think about olfactory coding, we also think our work leads to some important insights about the coding of complex natural blends that animals must recognize without prior experience. Please check it out to learn more.