How our brain organizes information about smells

The mysteries of the smell evaporate little by little. Recently, American researchers explained the brain mechanism that allows to perceive and distinguish odors. Anosmia, the loss of smell, in patients infected with Covid-19 has also been explained. In a new study, performed by neurobiologists at Harvard Medical School (HMS) and published in the journal Naturethe relationships between different odors coded in the olfactory cortex, the region of the brain responsible for processing odors, have been explained.

A neural system different than the perception of light and sound

The researchers managed to show that neural representations of smell in the cortex reflect the chemical similarities between smells, allowing scents to be categorized by the brain and can be ‘rewired’ through sensory experiences. These findings suggest a neurobiological mechanism that may explain why individuals have common but highly personalized experiences with smell. “We all share a common frame of reference with smellsconfirms the study’s lead author, Sandeep Robert Datta, a professor at HMS. You and I think lemon and lime smell similar and agree they smell different from pizza, but until now we didn’t know how the brain organizes this kind of information..”

Smell allows animals to identify the chemical nature of the world around them. Sensory neurons in the nose detect odor molecules and relay the signals to the olfactory bulb, a structure in the brain where the initial processing of odors occurs. The olfactory bulb transmits information to the piriform cortex, the main structure of the olfactory cortex, for more complete processing. Unlike light or sound, it is difficult to understand how the brain builds neural representations of the small molecules that transmit smell. Often, subtle chemical changes can lead to significant differences in odor perception. The results open up new avenues of study to better understand how the brain transforms information on the chemistry of odors into the perception of smell. “This is the first demonstration of how the olfactory cortex encodes information about the thing it is responsible for, which is the chemistry of smells, the fundamental sensory signals of olfaction.”, rejoices Sandeep Robert Datta.

Predict the identity of an odor

The researchers focused on the question of how the brain identifies related but distinct smells. For this, they developed an approach to quantitatively compare chemical odors. They used machine learning to examine thousands of chemical structures known to have odors and analyzed thousands of different characteristics for each structure, such as number of atoms, molecular weight, and electrochemical properties. This data allowed the researchers to systematically calculate how similar or different one odor was to another. This helped them design three sets of smells: one set with great diversity; one with intermediate diversity, with odors divided into related clusters; and one of low diversity, where the structures varied only by gradual increases in carbon chain length.

They then delivered odors with carefully selected molecular structures from the different sets to mice whose neuronal activity they analyzed. The experiments revealed that similarities in odor chemistry are mirrored by similarities in neuronal activity. Associated scents produced correlated neural profiles in the piriform cortex and olfactory bulb, measured by overlaps of neural activity. Weakly bound odors produced weakly bound activity patterns. In the cortex, associated scents led to more tightly clustered patterns of neural activity compared to patterns in the olfactory bulb. Cortical representations of odor relationships were so well correlated that they could be used to predict the identity of a retained odor in one mouse based on measurements made in another mouse.

Plasticity of the cortex, key to our differences

The researchers also found that these neural representations are flexible. The mice were repeatedly given a mixture of two scents, and over time the corresponding neural patterns of these scents in the cortex became more strongly correlated. This happened even when the two scents had different chemical structures. The cortex’s ability to adapt has been driven in part by neural networks that selectively reshape odor relationships. When the normal activity of these networks has been blocked, the encoded cortex smells more like the olfactory bulb. “We presented two smells as if they came from the same source and observed that the brain can reorganize itself to reflect passive olfactory experiencesobserved the researcher. Part of the reason things like lemon and lime smell alike is likely because animals of the same species have similar genomes and therefore similarities in smell perception..”

The plasticity of the cortex explains that despite all the similarities, each individual has a different perception of the same smell. “Plasticity of the cortex may help explain why smell is partly invariant between individuals, yet customizable to our unique experiences.”, confirms Sandeep Robert Datta. Further research is needed to identify these mechanisms more precisely. “We don’t yet fully understand how chemistries translate into perception, continues the researcher. There is no algorithm or computer machine that will take a chemical structure and tell us what that chemical will look like. To actually build this machine and one day be able to create a controllable, virtual olfactory world for a person, we need to understand how the brain encodes odor information. We hope that our results are a step in this direction.”, he concludes.