Thursday, August 20, 2020

Neuroplasticity and Olfactory Existentialism


New study reveals how the brain organizes information about odors

Jul 2020,


A study by neurobiologists at Harvard Medical School now provides new insights into the mystery of scent. Reporting in Nature on July 1, the researchers describe for the first time how relationships between different odors are encoded in the olfactory cortex, the region of brain responsible for processing smell.


The sense of smell allows animals to identify the chemical nature of the world around them. Sensory neurons in the nose detect odor molecules and relay signals to the olfactory bulb, a structure in the forebrain where initial odor processing occurs. The olfactory bulb primarily transmits information to the piriform cortex, the main structure of the olfactory cortex, for more comprehensive processing. [But] Often, subtle chemical changes—a few carbon atoms here or oxygen atoms there—can lead to significant differences in smell perception.


They use a database of physical and chemical features of tons of molecules, probably from the Dragon dataset, which is a relatively new set of thousands of chemical identities based on molar mass, chemical formula, chirality, boiling point, etc.


Then they choose three different synthetic odors, each one made of a group of different molecules, and each group having either very diverse features, intermediate, or minimal diversity. The minimally-diverse "odor" group could be made of molecules differing by only one carbon atom, for example.


Another way to think about these chemical combinations -- some are grouped close together in chemospace and some are spread out, where chemospace is a map of all the features in the dataset. It's like facespace, made of thousands of faces and mapping all the features against each other; eventually you will find the "eignenface" right smack in the middle of the map. These are both examples of an n-dimensional information space, where n is the number of features listed in the dataset. If your understanding of dimensionality stops at the common physical world of three-, then you will need to stretch for this one.


Mice then get exposed to each of these "odors" while their neural activity is observed using multiphoton microscopy. They found that low-diversity molecule-groups, ones that were very similar to each other in their chemical characteristics, were associated with clustered neuron patterns. For the inverse, an odor made of very different chemicals would excite neurons all over the place (chemospace x neuronspace). They also found that in general, certain chemical features could be matched with recognizable neuron activity patterns.


This sounds as if there is some universal olfactory attributes in the chemical compendium.


BUT, they also found that if they repeatedly presented the mice with any two chemicals paired together, then the corresponding neural patterns would become more strongly correlated, and despite how different those two chemicals were.


"The brain can rearrange itself."


And again, and in other words, olfaction is confusing:


"Part of the reason why things like lemon and lime smell alike, he added, is likely because animals of the same species have similar genomes and therefore similarities in smell perception. But each individual has personalized perceptions as well.


"The plasticity of the cortex may help explain why smell is on one hand invariant between individuals, and yet customizable depending on our unique experiences."

-Sandeep Robert Datta, associate professor of neurobiology in the Blavatnik Institute at HMS


(He also says the phrase "virtual olfactory world" in reference to a future that sounds very exciting, although still very far away.)


There's another study here which looks pretty similar. They offer a reiteration of this new explanation for how smells are perceived, and it sounds like this -- we all share a similar smell-space due to our shared genome. This is manifest in the olfactory bulb, and in the way that it codes individual odor molecules based on their physical and chemical properties.


They ask "Can distant odours be grouped together if their context is learned to be the same?" And that answer, because of studies like these, is becoming clearer by the day -- yes.


In fact, this is the basis of how olfaction works, why it works, and what it's supposed to be doing for us. The common association between chemical properties and neural activity is just a given. It's in that second layer, and over the course of a lifetime of being exposed to different combinations of chemicals, that our brain generates the end results, olfactory perception, which by its nature must be subjective, and because of the transient, vacillating and boundless parameter space of our ontogenetic chemical exposome. (Chemosome?) They call this pairing of chemical milieu and existential moment an odor "contingency," and they say these contingencies are what rewrite the higher olfactive network space.


Random fact: "The mouse initiates the trial by touching the lickometer." Yes, the lickometer.


Both of these are true; Yes there is a static, predetermined program that senses chemicals in the air in mostly the same way for all people (excepting genetic variation, which can be up to 30%). But there is another network layer found in the olfactory cortex where we all diverge from each other, and this next layer is based on our autobiography, for lack of a better word. Who we are and the decisions we make are changing this second layer with every new encounter.


Back to the study, their statement "Our results indicate that representations of categories emerge dynamically by mitral cells in a way that fits not only task demands but also categorical logic" is another way of saying that we can train our nosebrain to interpret any smell in any way we want. And again, "Once learned, these tasks allowed us to assign the same odour stimuli to different category schemes. If mitral cells activity reflect the learning rules, odour representations would change in a way that follows categorical information."


The point here is that our olfactory perception network is constantly changing, and that's why it's so hard to pin it down. And that's what it's supposed to do -- it's supposed to help us respond to our environment; but our environment is constantly changing. Society and culture, for example, can cause major shifts in both the chemical soup that surrounds us and in the way we semi-autonomously assign meaning to odor objects. See mint and analgesics in the postwar population of England, or licorice for the same age group, or the smell of "new car" in the East vs West.


Body odor, and especially the odor of others who do not eat the same food as you, or follow the same culturally inculcated hygiene rituals as you, will definitely smell "foreign" to you. Until you become more acquainted, of course, at which point it slowly becomes part of your identity also. You do not begin to smell that way, but because your olfactory translation machine no longer flags a smell as "foreign" if it's been around your neighborhood for the past ten years, or if it's been in your own bed for example. The brain can rearrange itself. 


So, smells are both objective and subjective. There is a common denominator to the perception of odor molecules, but depending on the infinite variations of exposure that accumulate over a lifetime, that common denominator is shredded, stretched, skewed and refit to match your personal experience in the olfactory multiverse.


And so to answer an age old question in olfactory research -- "Do odors have their own universal identity, or is our nosebrain a blank slate?" -- the answer is, "Yes."




Study 1 - Harvard Medical School

Stan L. Pashkovski et al, Structure and flexibility in cortical representations of odor space, Nature (2020). DOI: 10.1038/s41586-020-2451-1

[alt link]


Abstract: The cortex organizes sensory information to enable discrimination and generalization1,2,3,4. As systematic representations of chemical odour space have not yet been described in the olfactory cortex, it remains unclear how odour relationships are encoded to place chemically distinct but similar odours, such as lemon and orange, into perceptual categories, such as citrus5,6,7. Here, by combining chemoinformatics and multiphoton imaging in the mouse, we show that both the piriform cortex and its sensory inputs from the olfactory bulb represent chemical odour relationships through correlated patterns of activity. However, cortical odour codes differ from those in the bulb: cortex more strongly clusters together representations for related odours, selectively rewrites pairwise odour relationships, and better matches odour perception. The bulb-to-cortex transformation depends on the associative network originating within the piriform cortex, and can be reshaped by passive odour experience. Thus, cortex actively builds a structured representation of chemical odour space that highlights odour relationships; this representation is similar across individuals but remains plastic, suggesting a means through which the olfactory system can assign related odour cues to common and yet personalized percepts.


Study 2 - Hebrew University

Flexible Representations of Odour Categories in the Mouse Olfactory Bulb. Elena Kudryavitskaya, Eran Marom, David Pash, Adi Mizrahi. Hebrew University of Jerusalem. Mar 24 2020. BioRxiv. doi:


Summary: The ability to group sensory stimuli into categories is crucial for efficient interaction with a rich and ever-changing environment. In olfaction, basic features of categorical representation of odours were observed as early as in the olfactory bulb (OB). Categorical representation was described in mitral cells (MCs) as sudden transitions in responses to odours that were morphed along a continuum. However, it remains unclear to what extent such response dynamics actually reflects perceptual categories and decisions therein. Here, we tested the role of learning on category formation in the mouse OB, using in vivo two-photon calcium imaging and behaviour. We imaged MCs responses in naïve mice and in awake behaving mice as they learned two tasks with different classification logic. In one task, a 1-decision boundary task, animals learned to classify odour mixtures based on the dominant compound in the mixtures. As expected, categorical representation of close by odours, which was evident already in naïve animals, further increased following learning. In a second task, a multi-decision boundary task, animals learned to classify odours independent of their chemical similarity. BBBBBB Rather, odour discrimination was based on the meaning ascribed to them (either rewarding or not). Following the second task, odour representations by MCs reorganized according to the odour value in the new category. This functional reorganization was also reflected as a shift from predominantly excitatory odour responses to predominantly inhibitory odour responses. BBBBBB Our data shows that odour representations by MCs is flexible, shaped by task demands, and carry category-related information.

*In comparison to the above Harvard paper, for "mitral cells," read olfacotry bulb, and for "two-photon calcium imaging," read multiphoton microscopy.



Post Script:

Back to the "first layer" mentioned in the above studies, I need to mention what sounds to me like intensity being a big part of the universal "odor coder." It is certainly one of the chemical features in the corresponding dataset; odors tend to present to us in a known window of intensity, and each molecule has a detection threshold for humans measured in parts per million, billion or trillion. I'm not certain this is what's being implied and surely there's more complicated exclusions to it, but even prior research shows that intensity of an odor is a shortcut through a lot of these categorization and dimension-reduction attempts.


Next, this is nuts; pretty sure I've never seen this before -- "The general profile of excitatory vs. inhibitory responses by mitral cells changed with learning and task demands. In naive animals, most responsive cells (71%) responded by excitation to the odours (Fig. 6A,B). Following the learning of the 5-decision boundary task, the ratio of excitatory/inhibitory responses reversed. After learning, the majority (71.4%) of neurons now responded by inhibitory calcium transients to the odours (Fig. 6C,E). The ratio of inhibitory vs. excitatory responses reverted back to normal after retraining the mice on the 1-decision boundary task. Specifically, 73.3% of responsive neurons were again excitatory on day 18 (Fig. 6D,E). (The Hebrew U study)


So the "second layer," the one that adds the personal, subjective meaning to your odors, is all inhibition. It's dampening the neurons that were originally excited by this odor and based on universal chemical-genetic affinities, but now have to be quieted based on prior outcomes of interactions with it. It doesn't dampen everything, obviously, or else you wouldn't smell it at all (you mean like violets?), but it dampens enough that the overall pattern of the signal that finally does make it through can be dramatically different. You're literally evolving with every breath you take.



Compulsory Reference to the Greatest Work of Olfactory Philosophy Ever:

Hosek R J & Freeman W J (2001). Osmetic Ontogenesis, or Olfaction Becomes You: The Neurodynamic, Intentional Self and Its Affinities with the Foucaultian/Butlerian Subject. Configurations 9: 509–541.

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