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My nose is growing

Picture How We Smell – 2

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I posted my own version of molecules-to-nose-to-brain smell recognition in May. I based this new one on Nobel Prize work by Linda Buck and Richard Axel. I made up the first version just using what I remembered of neural nets and artificial intelligence in computers. Doctors Axel and Buck and their students worked more than 15 years to find out what really happens. Obviously, this is the one to remember. But I’m proud of how much I got right in the first one.

This figure is my combination of Figures 2, 6, 13 and 14 from Linda Buck’s 2004 Nobel Prize for Physiology or Medicine lecture. The action proceeds from lower left to upper right. Odor molecules enter the nose. They encounter odor receptors right at the top back of the nose. These odor receptors are cells with one end in the nose and the other end in the olfactory bulb of the brain. The cells in the olfactory bulb are called glomeruli. (Hey! Physiologists use a lot of Latin. Stay with me. It’s worth it.) Each of these glomeruli is a spherical collection point that sums up the outputs from hundreds or thousands of odor receptors.

The odor receptors and the glomeruli don’t recognize a flower or even a specific molecule in the flower’s smell. They recognize a piece of a molecule. One molecule may trigger responses from many odor receptors and one odor receptor may react to many different molecules. Figure 8 in Linda Buck’s lecture shows one molecule (in the 11th row down) triggering responses from 8 odor receptors. And one odor receptor (number 85) reacts to 8 different molecules.

The odor receptors and the glomeruli make up what I think of as the special purpose, smell-specific hardware. Depending on the species, there are a few hundred to about 1000 different types of each. One of each type of glomerulus collects signals from odor receptors in the left nostril. And there’s a duplicate set of everything for the right nostril. All the odor receptors of one type (e.g., the red lines in my picture) in one nostril go to just one collection point (the red oval in my picture).

The real work of recognition and memory and emotional response happens further into the brain, starting with cortical neurons in the olfactory cortex. Each of these neurons gets input from a bunch of glomeruli and each glomerulus sends output to many different cortical neurons. And the cortical neurons connect to each other. So a smell is recognized by a combination of signals and perhaps also by the absence of other signals. This is what artificial intelligence workers call a neural net. Buck and Axel call this combinatorial encoding of odor identities. As Buck says, “each OR serves as one component of the codes for many odorants. Different odorants have different ‘receptor codes.’ Given the number of possible combinations of 1000 different ORs, this combination coding scheme could allow for the discrimination of an almost unlimited number of odorants. Even if each odorant were detected by only 3 ORs, this scheme could potentially generate almost one billion different odor codes.” So much for the often quoted figure of 10,000 for the number of odors we can detect. We can do way better than that.

Vibration or Shape?
Linda Buck and Richard Axel gave their Nobel Prize lectures on December 8, 2004. Neither lecture said anything about whether the odor receptors react to the shape or vibrations of odor molecules. Luca Turin had published his version of the vibration theory in Chemical Senses 21, 773-791 (1996). By all accounts, his theory was not widely accepted. In April, 2004, Andreas Keller and Leslie Vosshall published three phychophysical tests of the vibration theory in Nature Neuroscience 17, 337-338, and concluded that none of the results supported the new theory. Buck and Axel’s work showed that the odor receptors are part of a much larger family of receptors that sense many kinds of molecules outside the cell and activate signals inside the cell. It’s believed that molecules penetrate a little into these receptors and cause them to change shape in a way that causes another molecule to detach from the receptor. Buck and Axel’s work shows that a single receptor reacts to only a part of a molecule and does not have to sense all its vibrational modes or all the atoms that make up its shape.

Does this help me tell lemon from lime?
The good news is, the odor receptors that stick out into your nose and that are vulnerable to damage are also replaced regularly. And there’s redundancy – remember the hundreds or thousands of copies of each type of odor receptor. So smelling too much ammonia, or chili or Grey Flannel probably won’t do long term damage. A cold probably just blocks access to the odor receptors – get the gunk out of the way and the molecules can get back where you want them.

Your genetics determines the odor receptors you have in your nose. Each receptor comes from a different gene. There are genetic differences from one person to another. According to the National Geographic smell survey (Oct., 1987, pp 514-525), the ability to detect a male pheromone, androstenone, varies from 63% of men in the US to 84% for women in Europe. Maybe the ability to smell is like the design of the heart and varies only a little from one healthy person to another. Maybe the people who easily detect androstenone have 1000 of each of the receptors they need. I’m about at the threshold – I can detect something but can’t characterize androstenone as smelling musky (or like anything at all). Maybe I only have 100 of each necessary receptor. Maybe the people who can’t smell it at all have 10 or fewer. Or maybe smell is like hair color and tissue type. Maybe some of us have brown eyes and just naturally like woody fragrances. Maybe natural blonds naturally prefer sweet and fruity. Nah - easy, sloppy thinking like that is almost always wrong.

One common kind of smell test measures the lowest concentration of a pure chemical that you can detect. I think that’s really dependent on the specific odor receptors you have and how many you have of each. But there are other smell tests: Can you tell which of three chemicals is different from the other two? Can you classify a smell as musky, floral, spicy, etc? Can you identify a citrus smell as lemon or lime? Does androstenone smell nice or nasty? All these involve processing by the general purpose neurons in the colorful upper right corner of my figure. These are like the logic bits in my computer’s microprocessor. I can use them to do mathematical operations, spell check this document, draw a new diagram, or find e-mail from last year. The earliest computers couldn’t do any of those things - but the basic logic elements carried all the possibilities.

As I write this I’m drinking a glass of 7 Up limited edition Diet Pomegranate. It’s red. And sweet. But for all I can tell it could be cherry, raspberry, cranberry or Hawaiian Punch. Helen Keller learned to smell a storm coming, “hours before there was any sign of it visible.” My brain has enough practice analyzing signals from my eyes that I can recognize the same famous American in all these images. So I hope to do better with training.


  1. lisa16's Avatar
    Oh cool post! And good for you on getting so much of it right by yourself!

    I used to teach a class from time to time on the meaning of food, and I always did a little experiement with the 7up you are drinking (well, the cherry one) to illustrate the realtionship between taste and smell. If you pinch your nose shut and drink it, it tastes like regular 7 up. But the split second you open your nose, you get the cherry. It is like magic. Chemical magic, in this case.

    I didn't realize you live in Texas! I lived in San Angelo for three years before moving back to my home state. Texas is its own very special place.


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