Wednesday, August 12, 2009

I smell a rat! (but how do I know it's a rat?)

There's a very fine review in the current issue of Nature Neuroscience, by Zou et al.; "How the olfactory bulb got its glomeruli: a just-so story?" These authors discuss one of the more fascinating genetic and developmental--and hence also evolutionary--topics we know of. It's one we dealt with in some length in The Mermaid's Tale, and even in our earlier book (2004, Genetics and the Logic of Evolution).

This new review paper deals with recent findings in studies of the way that the olfactory system, by which we detect, classify, and remember odors, works. There are many fascinating aspects of this system, some of them conserved even in insect olfaction (and we mentioned a few of the aspects that fascinate Richard Axel when we described his talk at Bar Harbor). Here we'll deal only with some generalizations, and we'll carry the discussion further in our next post, so we don't get too verbose here!

As we discuss in Mermaid's Tale, some sensory systems must retain a kind of direct representation, or 'topographic map', of the incoming information, for the simple reason that that information has some form of regular order. Vision is the detection of 2-dimensional streams of incoming light, 2-dimensional because they represent x-y coordinates of the light source (3-D vision is a separate topic that complicates this a bit, but doesn't alter this basic idea). Sound has a natural spectrum of frequencies, too.

These signals are perceived by neural systems that themselves have maplike representational properties. The retina is a surface of cellular receiving pixels, and the cochlea a linear (though coiled-up in many species, including ourselves) way to sense relative sound frequencies. Both retain their sensory 'map' of incoming signal as they send detection impulses to the brain.

Topographic neural maps are how we discern and keep track of the orderliness of the information from 'out there' at any given time, and this is also built by developmentally logical, orderly ways that in a sense take advantage of the orderliness of the information. As you move along the cochlea, sound-detecting hair cells respond to gradually changing frequencies, and they send their axons to the brain in this orderly way. Likewise as you look across the retina, like the pixels on a TV screen, the cells are receiving images from corresponding places in the incoming image.

Smell is different. Odors have no locational or other spatial properties. To detect a smell and remember it, you don't have to relate it spatially to other odors, or even to where it came from, except generally. But you do have to identify and remember it in some way!

The first and important (and intriguing) key to the way this has evolved is that there is a huge gene family, of about 1000 members in mammals, that codes for olfactory cell-surface receptor proteins (ORs) that bind to odor molecules. These genes are on almost all our chromosomes in clusters of from a few to tens of members (and because we're diploid each cell has two copies of these 1000 genes). Yet each neuron picks only one copy of one of these genes to use, so it only has one type of receptor on its surface--how this happens is not understood. The other 999 genes (both copies) are kept turned 'off'. (There are some partial exceptions to this, that show how the one-gene picture usually results).

This way only particular odor molecules can bind to each olfactory neuron (ON), triggering an 'I smell it!' message along its axon to the brain. In each OR gene cluster, the genes were produced by gene duplication and have similar DNA sequence and hence similar chemical binding properties. ONs in similar areas of the nose are more likely to express OR genes from the same cluster. But this is very patchy and incomplete and it also turns out that there is not a very systematic similarity in odor molecules the receptors coded by adjacent genes can bind.

This means that the ONs sending their axons to the brain don't have a particularly orderly map relative to any kind of odor spectrum, the way light and sound spectra are neurally mapped. Again, different odors don't have such a natural map. But once your brain's figured out 'lemon' or 'skunk', it remembers it, however it's mapped there, so that you can recall it the next time.

It was long thought that the axons of the ONs found their way to specific collecting points, called glomeruli, on their way to the brain, in a way guided by the OR receptors on their surface and that this was a way to concentrate the signal (if the pulse from all ONs that used the same OR and were thus detecting 'lemon' aroma molecules passed through the same glomerulus) and send it to some specified location in the brain.

But it turns out that this is only partly true. Instead of a fixed map, that we all share, we each seem to be placing our 'lemon' messages in different parts of the olfactory area of our brains. Again, so long as we each know where that is, we can recognize the next lemon that comes along. But your lemon is located in a different part of your neural garage than mine.

So, unlike vision and sound, where it appears each of us has a similar source-to-brain map, this seems not to be the case for smell, as Zou et al. review. In our next post we'll explain what does seem to happen because while it doesn't depend on a topographic map, it does reflect understandable, and hence evolvable, developmental mechanisms that enable our olfactory house to be in order.

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