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Sniffing out odor: How the brain organizes odor information

The 1960 premiere of the movie Scent of Mystery marked a singular event in cinema annals: the first and last movie picture debut “in glorious Smell-O-Vision.”

Hoping to wow moviegoers with a dynamic olfactory experience alongside the familiar sight and sound spectacles, select theaters were equipped with a Rube Goldberg-esque device that piped various scents directly to seats. Quickly, audiences and critics concluded that the experience had stunk. Smell-O-Vision was panned full of technical problems and became a running gag that holds a unique place in the history of entertainment.

Smell-O-Vision ‘s flop, however, failed to discourage entrepreneurs from continuing to pursue the vision of providing smells to consumers through digital fragrance technologies, especially in recent years.

Such attempts have produced press coverage but little progress, owing mainly to a restricted knowledge of how the brain converts odor chemistry into odor sensations — a process that for scientists in several respects remains elusive. Fresh insights into the nature of smell are now offered by a report by neurobiologists.

The researchers first explain how associations between specific odors are represented in the olfactory cortex, the brain area responsible for scent processing.

Through transmitting odors with specifically chosen molecular structures and observing neural behavior in awake mice, the team demonstrated that neuronal odor representations in the cortex constitute chemical odor similarity, helping the brain to classify scents into groups. Moreover, sensory experiences can rewire those representations.

The results indicate a neurobiological pathway that may clarify why people have specific yet extremely customized smelling experiences. “All of us share a common frame of reference with smells. You and I both think lemon and lime smell similar and agree that they smell different from pizza, but until now, we didn’t know how the brain organizes that kind of information,” said senior study author Sandeep Robert Datta, associate professor of neurobiology in the Blavatnik Institute at HMS.

The results open new avenues of study to better understand how the brain transforms information about odor chemistry into the perception of smell.

“This is the first demonstration of how the olfactory cortex encodes information about the very thing that it’s responsible for, which is odor chemistry, the fundamental sensory cues of olfaction,” Datta said.

The sense of scent helps animals to recognise the chemical essence of the natural environment. Within the nose, sensory neurons sense odor compounds and transmit messages to the olfactory bulb, a device in the forebrain where the actual perception of odor takes place. For more comprehensive processing, the olfactory bulb primarily transmits information to the piriform cortex, the principal structure of the olfactory cortex. Unlike light or sound, stimuli easily controlled by tweaking features such as frequency and wavelength, it is difficult to test how the brain builds neural representations of the small odor-transmitting molecules.

Subtle chemical modifications — here several carbon atoms or oxygen atoms — will also contribute to major variations in the sense of smell.
Datta, along with the first study participant Stan Pashkovski, neurobiology research fellow at HMS, and collaborators addressed this task by concentrating on how the brain detects similar yet separate odors.

“The fact that we all think a lemon and lime smell similar means that their chemical makeup must somehow evoke similar or related neural representations in our brains,” Datta said.

Further study, the researchers developed an method for quantitative analysis of odor chemicals similar to how, for example, variations in wavelength can be used to quantitatively evaluate light colors.

They used machine learning to look at thousands of chemical structures reported to have odors, and examined thousands of specific features for each form, such as atom size, molecular weight, electrochemical properties, and more. Together, these data allowed the researchers to determine systematically how close or different an odor was relative to another.

The team developed three collections of odors from this library: a collection of high diversity; one of moderate diversity, of odors separated into similar clusters; and one of low diversity, where configurations differed only through small variations in duration of the carbon chains.

They then exposed mice to different odor combinations from the different sets and used multiphoton microscopy in the piriform cortex and olfactory bulb to image patterns of neural activity.

The tests found differences in odor composition have been replicated in neuronal function by correlations. Similar odors culminated in associated neural trends in both the piriform cortex and olfactory bulb, as determined by neuron activation overlaps. By comparison, weakly associated odors generated weakly linked patterns of operation.

Related odors in the cortex led to more strongly clustered neural activity patterns as compared to olfactory bulb patterns. This observation was true across single mice.

Cortical interpretations of odor associations have become sufficiently well-correlated that they can be used to determine the presence of a hold-out odor in one mouse based on observations produced in another mouse.

Further analyzes defined a number of chemical characteristics such as molecular weight and other electrochemical properties which were related to neural activity patterns. Knowledge gleaned from these traits was versatile enough to model cortical reactions to an odor in one species based on studies with a different collection of odors in another.

Those neural representations were also considered versatile by the researchers. A mixture of two odors was regularly provided to mice, and over time the resulting neuronal associations of such odors in the cortex became more closely associated. This occurred even though there were dissimilar chemical compounds in the two odors.

The cortex ‘s capacity to adjust has been partly created by neuronal networks that selectively reshape odor connections. When such networks’ usual function was disrupted, the cortex encoded smelled more like the olfactory bulb.

“We presented two odors as if they’re from the same source and observed that the brain can rearrange itself to reflect passive olfactory experiences,” Datta said.

He explained that one of the explanation items like lemon and lime smell identical is possibly that individuals of the same genus have similar genes and thus differences in the detection of smells. But every single person also has personalized perceptions.

“The plasticity of the cortex may help explain why smell is on one hand invariant between individuals, and yet custommizable depending on our unique experiences,” Datta said.

Together the research findings reveal for the first time how the brain encodes odor connections. Compared with the fairly well-understood visual and auditory cortices, it is also uncertain whether the olfactory cortex translates odor chemistry information into scent experience.

According to the paper, understanding how olfactory cortex maps related odors now offers fresh perspectives that guide attempts to explain and ultimately regulate the sense of smell.

“We don’t fully understand how chemistries translate to perception yet,” Datta said. “There’s no computer algorithm or machine that will take a chemical structure and tell us what that chemical will smell like.”

“To actually build that machine and to be able to someday create a controllable, virtual olfactory world for a person, we need to understand how the brain encodes information about smells,” Datta said. “We hope our findings are a step down that path.”

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