Knowing Neurons
Brain BasicsSensation and Perception

How the Olfactory System Makes You Run Toward Pumpkin Spice Lattes, and Away From Rotting Flesh

By Ayushe Sharma and Brandon Mitchell

As you walk down the street towards your favorite coffee shop, you experience countless odors. Trash. Stale fries. Wet dogs. Floral perfumes. Overbearing colognes. Body odors paralleled by woody deodorant. Baby lotion. As you get closer to your destination, the aroma of delectable pastries and freshly brewed coffee dominates the air. What’s going on behind the scenes to allow your nose and brain to experience these scents? The answer to this question lies in the olfactory system.

The journey of an odor molecule begins with its release from a source. As the barista hands you a freshly brewed pumpkin spice latte, its tantalizing aroma is conveyed by thousands of small, volatile molecules known as odorant molecules. Once these molecules are released from the latte, they leave the cup, move through the air, and journey into your nose through your nostrils. Here, they encounter olfactory neurons, specialized cells of the nervous system armed with receptors that bind these odorant molecules (Mori, 2013). Olfactory neurons, and the cells that nourish them, can be found in tiny pits within the specialized patch of tissue (olfactory epithelium) lining the nasal cavity (Mori, 2013). From there, these signals are sent to the primary olfactory cortex, where they are processed and interpreted as the “smell” of your latte (Zhou et al., 2019).

These pieces are ultimately woven together to create a complex tapestry that serves as our mental representation of a smell.

The primary olfactory cortex is comprised of several brain regions, each with its own unique role in interpreting smells (Zhou et al., 2019). Each of these primary olfactory regions identifies and processes different components of the incoming signal. These pieces are ultimately woven together to create a complex tapestry that serves as our mental representation of a smell. The first stop is the olfactory bulb. Here, incoming signals from olfactory neuron receptors are broken down into their component parts (Mori, 2013; Pinto, 2011). Each olfactory receptor is tuned to a specific odorant molecule, and all of the cells expressing the same receptor protein are connected to the same glomerulus, which is a spherical bundle of cells, within the olfactory bulb. The glomerulus is both a sorting station and mixing pot for individual signals from the same type of olfactory receptor cell (Mori, 2013). Once signals reach the glomerulus, they collide, mix, and mingle to give us the unique combinations of aromas that the nose can recognize as different “smells.” From there, these signals are routed to the piriform cortex, which is responsible for identifying and distinguishing the subtle nuances of the smell (Bao et al., 2016; Bensafi, 2012). Ultimately, the concerted efforts of these regions allow us to recognize the unique combination of cinnamon, pumpkin, and nutmeg that make up the aroma of a pumpkin spice latte.

The AON-hippocampal connection is essential for linking smells to specific memories…

The olfactory bulb also sends these signals to the anterior olfactory nucleus (AON). The small yet mighty AON is an odor navigator that precisely pinpoints the origin of odors by using reference signals from both nostrils (Kikuta et al., 2010). The AON sends signals to the hippocampus, serving as a bridge between the brain’s smell and memory centers (Aqrabawi and Kim, 2018; Oettl et al., 2016). As it turns out, the AON and the hippocampus share a unique evolutionary history, which may be why they collaborate to help us form odor-related memories (Aqrabawi and Kim, 2018; Oettl et al., 2016). The AON-hippocampal connection is essential for linking smells to specific memories in time and space. The AON provides a spatial context for odors, while the hippocampus provides the temporal context. Have you ever noticed how a particular smell can take you back to a particular time or place — sort of like a time machine? For example, the smell of pineapples and coconuts might transport you to the week you spent in Krabi having coconut pineapple cocktails. The AON-hippocampus connection is what links these aromas to these memories, allowing you to vividly recall the smells and sensations of a particular moment. The hippocampus works in tandem with the orbitofrontal cortex (OFC), a region of the frontal lobe, to help you attribute the cinnamon-y aroma to the latte (rather than the paper cup that encases it), and plan your decisions accordingly (Li et al., 2006). So, the AON helps you identify where smells originate, the hippocampus helps you remember where smells originate based on your experiences. The OFC then uses this information to guide your decision-making process when faced with a new or unfamiliar smell.

Now, fast forward to several hours later, when you visit a new friend’s home for the first time. Upon entering the kitchen, you are immediately met with a putrid smell that causes you to recoil. This is no ordinary smell; it is the unmistakable stench of death and decay. Since this is a potentially dangerous odor, your brain triggers and immediate response that is orchestrated by the amygdala, the brain’s fear center and a key component of the primary olfactory system (Krusemark and Li, 2012). The amygdala relays these signals to the hypothalamus, activating the autonomic nervous system to prepare you for fight or flight. Since your hippocampus and orbitofrontal cortices are already familiar with this smell, they step in and remind you that you know this smell all too well (Gottfried et al., 2004; Li et al., 2006; Aqrabawi and Kim, 2018; Oettl et al., 2016). In a split second, you recognize it: the stench of rotting shrimp. The smell may not be pleasant, but it’s far less concerning than if it had a more sinister source.

The process of smelling something, called “olfaction,” whether it’s the delightful aroma of pumpkin spice lattes or the awful odor of decaying flesh, happens in a matter of milliseconds. This is because olfaction is the only sense conferred by a direct connection between the site that receives environmental signals (the nose) and its target brain region, without first passing through the thalamus, the sensory relay station used by our other primary senses. This structural feature allows us to quickly detect odorant warnings, such as rotting fruit or smoke. However, the direct connection between the outside world and our olfactory neurons, as well as the flurry of invaders and respiratory illnesses that can obstruct the nose, also makes this system especially vulnerable to damage. Anosmia, the inability to smell, occurs when olfactory neurons are damaged or destroyed (Reichert and Schöpf, 2018). Thankfully, unlike the neurons involved in our ability to see and hear, olfactory neurons are constantly being replaced throughout our lives. Every 5-8 weeks, new neurons migrate up into the olfactory bulb to replace old neurons that have died off. This means that patients with acute anosmia may regain their sense of smell as new neurons take the place of the old ones.

… your olfactory system is constantly working to help you relish life, maintain memories, and stay safe.

So, the next time you’re walking down the street and take a deep breath, take a second to appreciate the power of your olfactory system. Whether you’re experiencing the pleasant aroma of fresh flowers or the pungent smell of gasoline, your olfactory system is constantly working to help you relish life, maintain memories, and stay safe.

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Written by Ayushe Sharma & Brandon Mitchell
Illustrated by Melis Cakar
Edited by Anastasiia Gryshyna, Lauren Wagner, and John Zhou

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References

Aqrabawi, A. J., & Kim, J. C. (2018). Hippocampal projections to the anterior olfactory nucleus differentially convey spatiotemporal information during episodic odour memory. Nature Communications, 9(1), 1-10. https://doi.org/10.1038/s41467-018-05131-6

Bao, X., Raguet, L.L.G., Cole, S.M., Howard, J.D., Gottfried, J. (2016). The role of piriform associative connections in odor categorization. eLife, 5. https://doi.org/10.7554/ELIFE.13732

Bensafi, M. (2012). The Role of the Piriform Cortex in Human Olfactory Perception: Insights from Functional Neuroimaging Studies. Chemosensory Perception, 5, 4-10.

Gottfried, J.A., Smith, A.P.R., Rugg, M.D., Dolan, R.J. (2004). Remembrance of Odors Past. Neuron, 42(4), 687–695. https://doi.org/10.1016/S0896-6273(04)00270-3

Kikuta, S., Sato, K., Kashiwadani, H., Tsunoda, K., Yamasoba, T., Mori, K. (2010). Neurons in the anterior olfactory nucleus pars externa detect right or left localization of odor sources. Proceedings of the National Academy of Science. https://doi.org/10.1073/pnas.1003999107

Krusemark, E.A., Li, W. (2012). Enhanced Olfactory Sensory Perception of Threat in Anxiety: An Event-Related fMRI Study. Chemosensory Perception, 5(15), 37–45. https://doi.org/10.1007/S12078-011-9111-7

Li, W., Luxenberg, E., Parrish, T., Gottfried, J.A., (2006). Learning to Smell the Roses: Experience-Dependent Neural Plasticity in Human Piriform and Orbitofrontal Cortices. Neuron, 52, 1097–1108. https://doi.org/10.1016/J.NEURON.2006.10.026

Mori, I. (2013). Olfaction. Brenner’s Encyclopedia of Genetics: Second Edition, 161–163. https://doi.org/10.1016/B978-0-12-374984-0.01088-3

Oettl, L.L., Ravi, N., Schneider, M., Scheller, M.F., Schneider, P., Mitre, M., da Silva Gouveia, M., Froemke, R.C., Chao, M. V., Young, W.S., Meyer-Lindenberg, A., Grinevich, V., Shusterman, R., Kelsch, W., (2016). Oxytocin Enhances Social Recognition by Modulating Cortical Control of Early Olfactory Processing. Neuron, 90, 609–621. https://doi.org/10.1016/J.NEURON.2016.03.033

Pinto, J.M. (2011). Olfaction. Proceedings of the American Thoracic Society, 8, 46. https://doi.org/10.1513/PATS.201005-035RN

Reichert, J.L., Schöpf, V. (2018). Olfactory Loss and Regain: Lessons for Neuroplasticity. Neuroscientist, 24, 22–35. https://doi.org/10.1177/1073858417703910

Zhou, G., Lane, G., Cooper, S.L., Kahnt, T., Zelano, C. (2019). Characterizing functional pathways of the human olfactory system. Elife, 8. https://doi.org/10.7554/ELIFE.47177

Author

  • Ayushe Sharma

    Ayushe Sharma is a PhD candidate in the Departments of Neurology and Neurobiology at the University of Alabama at Birmingham (UAB). She uses brain imaging to map brain temperature and study neuroinflammation in patients with seizure disorders. Ayushe’s scientific pursuits outside the lab strive to make science more accessible to the lay public. She leads UAB’s Brain Core journal club, and also organizes the Brain Awareness Week celebrations in Birmingham, Alabama. In her spare time, Ayushe is a mixology enthusiast, vegetable gardener, and hobby artist.

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Ayushe Sharma

Ayushe Sharma is a PhD candidate in the Departments of Neurology and Neurobiology at the University of Alabama at Birmingham (UAB). She uses brain imaging to map brain temperature and study neuroinflammation in patients with seizure disorders. Ayushe’s scientific pursuits outside the lab strive to make science more accessible to the lay public. She leads UAB’s Brain Core journal club, and also organizes the Brain Awareness Week celebrations in Birmingham, Alabama. In her spare time, Ayushe is a mixology enthusiast, vegetable gardener, and hobby artist.