Monday, December 8, 2008

Tasty Wheat

Mouse: Do you know what it really reminds me of? Tasty Wheat. Did you ever eat Tasty Wheat?
Switch: No, but technically, neither did you.
Mouse: That’s exactly my point. Exactly! Because you have to wonder: How do the machines know what Tasty Wheat tasted like? Maybe they got it wrong. Maybe what I think Tasty Wheat tasted like actually tasted like oatmeal, or tuna fish! That makes you wonder about a lot of things. You take chicken, for example: Maybe they couldn’t figure out what to make chicken taste like — which is why chicken tastes like everything.
The Matrix, 1999

It comes off as inane commentary, the kind of maddening banter you get whenever people are confined together by duty, incarceration, or happenstance (and which may be one reason military rifles almost always have safety switches). But in fact the doomed Mouse’s immortal lines touch on a classic question that has long plagued philosophers.

How do I know that your experience of a thing is anything like mine?

Well, olfaction scientists have an answer to the Tasty Wheat Conundrum, and — talk about maddening — the answer is, “It depends.”

I’ve gotten ahead of myself again. Let’s start, as we often do, with Buck & Axel’s Nobel-winning work on the genes that produce the olfactory receptor proteins. Conceptually, the sense of smell starts out with a simple step: Vertebrates can identify many thousands of smelly chemicals in the air because they make around a thousand different versions of the protein sensor that sits on olfactory neurons. One odorant (or a small family of odorants) tweaks one type of receptor, which in turn is present on only one family of olfactory neurons. When those neurons fire, the brain knows that, say, acetic acid (basically, distilled vinegar) is in the air.

It’s a little more complicated than that: Actually one molecule can have several parts that activate different odorant receptors. But the pattern of olfactory neurons set in a tizzy by a single odorant molecule will be constant, and unique to that molecule.

So far so good: If everybody has the same receptor(s) for the aroma of Tasty Wheat, then at that level at least everybody is tasting the same thing (smell accounts for most of the variety of “flavors” we experience).

The next step in the sense of smell is when the olfactory neurons in the nose tweak the olfactory bulb in the brain. The OB is the central routing station for all smells; it coordinates the signals coming in from the nose, and may in addition enhance those signals — for example, as a powerful amplifying system for detecting faint odors.

Every olfactory neuron with the same receptor reports to the same glomerulus — a little ball of relay neurons that sends the signal up to the higher brain — in the OB, and each glomerulus gets signals from only one type of olfactory neuron. They map perfectly, one-to-one.

This is where things get messy, and a new report by Kimberly Grossman and colleagues at my wire-mommy Alma Mater, the University of Chicago, doesn’t make it any cleaner. But it does raise some interesting questions.

What the Chicago Five did was use sophisticated imaging of glomerular activity in concert with some old-fashioned mousie-chooses behavioral experiments (thanks, I’m guessing, in part to collaborator Leslie Kay, an extremely interesting lady who I’ve written about in the U of C Magazine) to compare what a mouse was doing to what its brain was doing.

One question they wanted to answer was whether a behavioral pattern in odor perception called a configural percept exists at the neural level. A configural percept is what happens when a mixture of chemicals that smell similar to each other add up to a completely different smell. Its opposite is an elemental percept, in which different-smelling odorants retain their individual smells when mixed together.

We know these phenomena exist at some level, because humans report them and mice act as if they experience them, too. But when Grossman and her homeys compared simple mixtures of two smelly molecules — pentanal and hexanal (two very similar odorants that arise from hamster litter, and which contribute to the smell of old rice) — elemental percepts depended on the exact mixture, and configural percepts were nowhere to be found. Worse, what was happening in the OB didn’t seem to bear much relationship to how the animals were reacting.

When they tested Mickey’s and Minnie’s ability to recognize the components of a mixture after being trained to spot the mixture, that ability depended on the ratio of the two components. With ratios of pentanal to hexanal smell that were equal to higher-on-the-pentanal-side, the response was purely elemental. Despite the fact that the two odorants were similar, animals trained on these mixtures were able to recognize either component on its own, no problem.

When hexanal smell outweighed pentanal, though, something very different happened: It was as if the mixture no longer contained pentanal, all the mice could smell was the hexanal. This overshadowing percept wasn’t expected.

Things got even loosier-goosier when they looked at the animals’ brains. The pattern of the glomerular activity of the olfactory bulb paralleled the behavior for the elemental percepts -- the pattern of glomeruli activated by the mixture looked pretty much like adding together the glomeruli activated by each separately. But the glomeruli for poor ol’ overshadowed pentanal were firing like crazy even when its smell was in the minority — and when the mice were acting like they couldn’t smell it.

We already suspected that the higher brain mucks up perception of smells — Proust’s over-cited cookie fetish works both ways, odors don’t only trigger powerful memories, memories exert powerful influence on how we experience odors. What this report shows is that there’s even a gap between the brain’s first processing step and what comes afterward. That gap may yet contain a one-to-one translation of chemistry to perception, but it doesn’t seem all that likely.

So let’s split the difference: At the level of hardware we share with snails and insects, my Tasty Wheat tastes like your Tasty Wheat. But once we move beyond the level of brain structures we share with lizards or fish, maybe my Tasty Wheat is your tuna fish.

Think on that over your morning cereal. But try not to irritate your cellmates.


Mickey Bricks said...

I love your blog, I love the Matrix and I love the way you write.

One problem though, we don't smell shapes; as the protein theory would have us believe, we smell vibrations.

Keep up the terrific job.

check in on my blog from time to time, its not exactly appealing to a Harvard grad such as yourself and nothing to do with dog olfaction, just a bit of fun: Smell o vision

Ken Chiacchia said...

First, thanks for the comment. I don't read nearly enough blogs, but I will check yours out.

Respectfully, though, depending on how you define the vibration theory it's either an 18th-century idea with scant evidence to support it, or just a restatement of what we know about all chemistry (everything is based on the movement of electrons).

If I said we recognize "shapes," I was engaging in a bit of poetic license, so let me clarify. What we recognize, of course, is chemistry, which is a combination of shape, hydrophobicity, charge, etc. As readers have already pointed out the idea that an odorant fits a receptor like a lock fits a key is an oversimplification -- but there are a mountain of data supporting chemical complementarity, and if vibration is to gain any real traction it's going to have to have more going for it than what I've seen so far.

The idea that odor receptors work differently from all other molecular sensors, including their closest conceptual relatives, the immunoglobulins and liver enzymes, is going to have to be very strong indeed. But hey, it happens sometimes. More data never hurt.

Anonymous said...

When I was a kid I came up with the question, "What if the color you and I both call green doesn't actually look green to you, but what I would call red?" There doesn't seem to be any way to test it. I therefore just depend on similar biochemistry and Occam's Razor and stop thinking about it.

beeman said...

I don't see what the issue is here - the OSN patterns don't match percptual difference s- BUT do you really expect to see mixture interaction at this level? Unless we are specifically talking about antagonists at the receptor site. But imaging studies in drosophila has recently shown that patterns in OSNs - look like simple additionas of componant patterns, but patterns in the PNs look very differney - why? Because mixture interactio is occuring at this level - post synaptically between OSNs and projection neurones (inverts that is). Its no surpirse that OSN activantion patterns og hex/pentanal mixture indicates thgat pental should be able to be smelkt. simply beause the inhibition hasnt occured yet. I'd like to see imagaging studies performed post synaptically for these odours.