New model show how the brain is organized to process odor information

March 19, 2012
Glomeruli in the olfactory bulb (shown in green), the first waystation for incoming olfactory signals, play an important role in the processing and identification of smells. Credit: Courtesy of Limei Ma, Stowers Institute for Medical Research

Just like a road atlas faithfully maps real-word locations, our brain maps many aspects of our physical world: Sensory inputs from our fingers are mapped next to each other in the somatosensory cortex; the auditory system is organized by sound frequency; and the various tastes are signaled in different parts of the gustatory cortex.

The olfactory system was believed to map similarly, where groups of chemically related odorants - amines, ketones, or esters, for example - register with clusters of cells that are laid out next to each other.

When researchers at the Stowers Institute for Medical Research traced individual odor molecules' signal deep into the brain, they found evidence that this "chemotopic" hypothesis of olfaction is insufficient, paving the way for a new model of how the sense of smell works, and how it came about.

"When we mapped the individual chemical features of different odorants, they mapped all over the olfactory bulb, which processes incoming olfactory information," says Associate Investigator C. Ron Yu, PhD, who led the study published in this week's online edition of the . "From the animal's perspective that makes perfect sense. The chemical structure of an odor molecule is not what's important to them. They really just want to learn about their environment and associate olfactory information with food or other relevant information."

The brain receives information about odors from olfactory receptors, which are embedded in the membrane of in the . Any time an odor molecule interacts with a receptor, an electrical signal travels to so-called glomeruli in the olfactory bulb. Each receives input from olfactory expressing only one type of olfactory receptor. The overall glomerular activation patterns within the olfactory bulb are thought to represent specific odors.

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Any time an odor molecule interacts with an olfactory receptor in the nasal cavity, an electrical signal travels to so-called glomeruli in the olfactory bulb. Each glomerulus receives input from olfactory receptor neurons expressing only one type of olfactory receptor. The overall glomerular activation patterns within the olfactory bulb are thought to represent specific odors. Credit: Courtesy of Limei Ma, Stowers Institute for Medical Research

"Chemotopy is a very attractive model," says Yu. But it had never been mapped accurately based on the earlier available technologies and recent experiments suggested that the chemotopic hypothesis breaks down at a fine level. To increase the resolution of the "olfactory map," Yu and his team generated a new line of transgenic mice with superb sensitivity and devised equipment that allowed them to deliver hundreds of odor stimuli to a single mouse.

When the Stowers researchers examined the activation pattern at the level of single glomeruli, they found that certain odors activated glomeruli within a distinct area of the , while others signaled to glomeruli located all over the map. Odors from different classes intermingled, too, suggesting that the glomeruli have not evolved to only detect the chemical shapes of specific odorants.

This makes sense, as there are hundreds of thousands of odors, says Limei Ma, PhD, a research specialist at Stowers and first author on the new study. "Many of them could be really novel to the organism, something they never encountered before," she says. "The system must have the capability to recognize and encode anything."

So if glomeruli didn't have a fidelity to certain molecular shapes, as the chemotopic hypothesis had suggested, what did unite them? The team was led to a "tunotopic" hypothesis of the olfactory system. Individual are "tuned" during evolution not to one particular kind of odorant, but to a variety of molecules. In combination, these receptors can then respond to those millions of smells. Glomeruli with similar tuning properties tend to be near each other. From a computing standpoint, this arrangement helps to enhance contrast among similar odors, explains Ma.

"The evolution of these receptors is not dictated by the chemical structures that they recognize," says Yu. "Most of our receptors have descended from a few common ancestral genes. Initially, they are more likely tuned to similar odors. When receptors accumulate mutations, it adds to their repertoire of natural odors they recognize."

Imagine a roomful of musicians. In chemotopy, the musicians are clustered according to their instruments and never play with other instruments. The team's tunotopic hypothesis is closer to an actual symphony: Different instruments overlap to create many more different sounds than the individual ones could.

Yu and his team think, further, that the tunotopic hypothesis may help us understand visual, auditory, and somatosensory processing as well. In the case of olfaction, tunotopy allows the animal to better distinguish among the nuances of odors. That precision, from an evolutionary perspective, would come in handy as the animal sorted through its environment.

It also helps us adapt to a constantly changing world.

"When you have a new chemical synthesized, like new perfumes and food flavors, you don't have to create new brain regions to react to it," says Ma. "What you do is use the existing receptors to sense all these chemicals and then tell your brain whether this is novel, whether it's similar, or whether it's something really strange."

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not rated yet Mar 20, 2012
The "tuning" are ALL the associations of ALL perceptual senses of neuronal activity delivered to the brain and occurring during an physical event. The permutations of these associations - you call them "In combination" leads to a persons' unique label of any odor.

What is the "tunotopy" hypothesis???

There is Fourier (analysis) to explain literally everything that goes on with and within the human auditory process - from the ears to the molecular/cellar processes in the ears and brain.

"The evolution of these receptors is not dictated by the chemical structures that they recognize," says Yu.

Sorry, Yu. You are going to retract that statement.

That's like saying:

"The evolution of auditory receptors are not dictated by the sounds that they recognize." says Yu.

You are wrong. You are wrong. You are wrong.
Retract that statement. The last advice you will ever hear before you embark on a path of no return.

not rated yet Mar 20, 2012
Human pheromones and food odors: epigenetic influences on the socioaffective nature of evolved behaviors in the current issue of Socioaffective Neuroscience & Psychology details how this tuning occurs across species from microbes to man as is already predicted by what is neuroscientifically known about olfactory/pheromonal input associated with other sensosy input. http://www.socioa.../current
not rated yet Mar 25, 2012
Wow, Firstly Tausch, all Yu means by "The evolution of these receptors is not dictated by the chemical structures that they recognize," is that they the odorant receptors have 'broad substrate specificity' - meaning that due to the incomprehensible combinations of odors one organism would be exposed to, and expected to perceive for survival- the odorant receptors (ORs) must have evolved to recognize various odorants i (the ligand molecules which comprise odors)- all with their unique molecular shape, in combination and alone - thus why the perception of the odor is dictated by the glomeruli pattern of activity.
not rated yet Mar 25, 2012
NOT THE RECEPTOR- SECONDLY, comparing ORs to Auditory receptors is bogus. Do you know your auditory anatomy? There are kinocilia and stereocilia positioned on different portions of the tectorial membrane of the organ of corti- their position dictates what frequency of sound they respond to and conduct action potentials down the auditory nerve. Sound has 4 identifying characteristics to perceive :pitch, timbre, location and loudness... Thats 4 versus ALL of the odors on earth, in endless combinations. Hence, your analogy is completely unfounded.
not rated yet Mar 27, 2012
Odor receptors provide a clear evolutionary trail that can be followed from microbes to man. Nutrient chemicals and pheromones are associated with other sensory input that is collectively linked to intracellular signaling and stochastic gene expression as appears to occur with OR genes. Isn't this what allows for the suggested tuning? If so, the tuning may occur without other sensory input in organisms with no olfactory bulbs, ears, or eyes, and "tuning" allows for the evolution of species with olfactory bulbs, ears, and eyes. Forget the analogies for a minute, and focus on evolution's sensory drive. Analogies are not determinants of biologically based behavior, olfactory/pheromonal input is. For contrast, however, we could make everything about the development of human sexual behavior seem to depend on visual and auditory input. Is there a model for that?

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