The sense of smell is powerful for its ability to evoke a
response to a past experience, whether it was experienced
years ago or an hour ago. This could be associated with a
cooked dinner, a hike in a forest after rain, or the stench of
garbage in a city alleyway. Yet the association between a
smell and the memory surrounding it leaves many
unanswered questions about the process and the ways it is
used in people. For example, one may wonder whether
infants experience the same sort of memory retrieval due to
olfactory stimulus that adults do, or what changes occur in
the brain as a result of loss of the ability to smell. It is
important to note that the reason our senses are such
powerful tools lies in their connections to the brain; since our
brain is perhaps the least understood organ, we already
have a sense of its vast complexity and capability for what
may be the unthinkable. While it may seem simple in nature
that we have memories associated with smell, this trait can
leave a large impact on us as we grow older. It is also this
property that is exploited commercially by fragrance
companies to make scents more appealing to consumers.
Because the brain has certain effects and capabilities in
response to various stimuli, we are also able to compare
these responses to other signals and how they differentiate
from smell - in other words what makes smell special to us.

   In order to better understand the process of connecting a
scent with the brain, we can begin by asking: how does the
brain take apart scents to process them? To answer we
must look first in the nose and olfactory bulbs. The olfactory
bulb is a part of the forebrain and is equipped with a set of
nerves that extend past the Cribriform plate – a part of the
Ethmoid bone that is located between the eyes – into the
nasal cavity. When receptors in the nose pick up molecules
from a specific scent, it is transmitted as an electrical signal
to the olfactory bulb (Manzini et al., 2014). In order to
perceive something as a smell, the molecule must be an
odorant, meaning it must meet some criteria, typically having
some hydrophobicity and volatility (Mayhew et al., 2022).
The human nose is said to have approximately 350 different
receptor types which can react to various smells through
their molecular components (Rinberg, 2020). Olfactory
receptors operate such that any combination of odor
molecules can activate different sets of receptors (Malnic et
al., 1999). The molecules’ recognition and interaction with
the receptors operates in a combinatorial way (Malnic et al.,
1999). This results in a system of activation allowing one to
recognize what is now estimated to be up to 1 trillion
different odors (Bushdid et al., 2014).

 Since the glomeruli, nerve ending bulbs found in the
olfactory bulb, are unique to interactions with different smells,
our perception of smell is highly dependent on how well they
are activated and in what order. As a result, if we switch up
the sequence in which they are activated or inactivate some
of the receptors, we are likely to have a loss in ability to
sense odors. One experiment testing this phenomenon of
sequential activation impact on recognition was completed
using a mouse model, which found that a delay or an
interruption of a specific receptor receiving an orderant would
decrease the system of cooperation between the receptors
(NYU Langone Health, 2020). It was found that through the
changing of the first glomeruli activated, as much as 30% of
a drop could be recognized in the ability of a mouse to
correctly sense the odor signal (NYU Langone Health, 2020).
By contrast, if the last of the glomeruli was changed, only
about 5% would be potentially dropped in the ability of the
mouse to sense the correct odor. (NYU Langone Health,
2020). In order to identify what odors stand out within a
mixture as well, the right sensors must be activated in the
right order and time. Any deviation in either of these abilities
would result in the decreased ability to recognize and
categorize the smell accurately. Following this transmission
of electrical signals to the glomeruli they will proceed to the
brain’s cortex (NYU Langone Health, 2020).

   Once the signal reaches the neurons of the cortex the brain
takes further action. The piriform complex, a set of neurons
right behind the olfactory bulb, will work in attempts to
recognize the smell itself. This complex is the only known
structure other than the hippocampus to have a three-layered
allocortical structure, and is activated when the pyramidal
cell, a type of neuron, receives information from the glomeruli
and transmits it to other regions of the brain (Vaughan,
2014). This also helps with responses to specific odor
mixtures by aiding in the formation of a neural network that is
capable of reliably transmitting these messages. The anterior
piriform complex is thought to hold information of the
molecular features of the odorant, whereas the posterior
piriform for the quality of the odor (Gottfried, 2006). The
piriform complex additionally is used to help differentiate
odors (Howard et al., 2009) and is involved with the working
memory where the odor information can be temporarily
stored (Zelano et al., 2009). In other words, it is of crucial
importance that this complex is responsive and active in
order to retain a highly functioning smell identification and
memory connection system. It is from this complex that the
information can then be further passed over to other areas of
the brain.

Laura Kilikevicius
Olfactory Responses by Memory 

20Brain Matters・Volume V Issue ii



 Having left off in our pathway at the piriform complex,
various cells within this structure will signal and move the
information to the thalamus, a complex key for translating the
neural impulses that come from the receptors to the cerebral
cortex. It is also important for various sensorimotor
association functions, including motor activity, emotion, and
memory, among others (Blumenfeld, 2018). From the
thalamus, the information can be passed to multiple
locations, including the hippocampus. This area is a key part
of the brain that stores information involved with learning and
memory, and is a crucial component of the olfactory system
for this connection to memory. When the neurons signal to
the amygdala, the portion of the brain involved with emotion,
they are able to activate it in ways that depend highly on the
pleasantness of smell to the individual (Zald & Pardo, 1997).
The location of the amygdala is what helps make the
association between memory and smell so strong (Walsh,
2020). The amygdala portion of this process contains a
series of steps that refine the process, and since the olfactory
bulb also signals directly to the limbic system, it is easy to
register the emotions that are in close coordination with the
smells encountered. Analyzing how the sense of smell is
associated with memory therefore very closely is related to
the location of the centers in the brain that will respond. Since
the amygdala is so involved in the olfactory response, an
expected response of emotional connection and memory
creation/retrieval is bound to occur. Just as how some people
associate a certain smell with a bad memory, the brain links
various memories with the senses experienced resulting in
these unfortunate retrievals. In a similar manner, we can
experience positive emotions with a particular smell, and both
of these examples would include many different interactions
of the brain to create the overall sensations that we
experience. The combination of memory and smell is one
that is unique in many ways for its strong connections with
multiple key areas of the brain and the ability to recognize an
abundance of smells.

   To smell an odor does much more than evoke a particular
memory, despite being an important emotional contribution to
the human experience. It has the capability to create
 connections and respond in ways in the brain that are
stronger than previously thought while being a crucial
contributor to our brain function.

   The sense of smell is powerful for its ability to evoke a
response to an experience, whether it was experienced years
ago or an hour ago. This could be associated with a cooked
dinner, a hike in a forest after rain, or the stench of garbage
in a city alleyway. However, the association between a smell
and the memory surrounding it leaves many unanswered
questions about the process and how it is used in people. For
example, one may wonder whether infants experience the
same sort of memory retrieval due to olfactory stimulus that
adults do or what changes occur in the brain due to losing the
ability to smell.

 Our senses are such powerful tools because of their
connections to the brain; since our brain is perhaps the least
understood organ, we already have a sense of its vast
complexity and capability for what may be unthinkable. While
it may seem straightforward that we have memories
associated with smell, this trait can significantly impact us as
we grow older.This property is also exploited commercially by
fragrance companies to make scents more appealing to
consumers. Because the brain has specific effects and
capabilities in response to various stimuli, we can also
compare these responses to other signals and how they
differentiate from smell - in other words, what makes smell
unique to us. 

   In order to better understand the process of connecting a
scent with the brain, how does the brain take apart scents to
process them? To answer, we must look first into the nose
and olfactory bulbs. The olfactory bulb is a part of the
forebrain and is equipped with a set of nerves extending past
the Cribriform plate – a part of the Ethmoid bone located
between the eyes – into the nasal cavity. When receptors in
the nose pick up molecules from a specific scent, it is
transmitted as an electrical signal to the olfactory bulb
(Manzini et al., 2014). In order to perceive something as a
smell, the molecule must be an odorant, meaning it must
meet some criteria, typically having some hydrophobicity and
volatility (Mayhew et al., 2022). The human nose is said to
have approximately 350 different receptor types, which can
react to various smells through their molecular components
(Reinberg, 2020). Olfactory receptors operate such that any
combination of odor molecules can activate different sets of
receptors (Malnic et al., 1999). The molecules' recognition
and interaction with the receptors operate combinatorially
(Malnic et al., 1999). This results in a system of activation
allowing one to recognize what is now estimated to be up to 1
trillion different odors (Bush did et al., 2014).

   Since the glomeruli, nerve-ending bulbs found in the
olfactory bulb, are unique to interactions with different smells,
our perception of smell depends on how well they are
activated and in what order. As a result, if we switch up the
sequence in which they are activated or inactivate some of
the receptors, we will likely lose the ability to sense odors.
One experiment testing this phenomenon of sequential
activation impact on recognition was completed using a
mouse model, which found that a delay or an interruption of a
specific receptor receiving an orderant would decrease the
system of cooperation between the receptors (NYU Langone
Health, 2020). It was found that by changing the first
glomeruli activated, as much as 30% of a drop could be
recognized in the ability of a mouse to correctly sense the
odor signal (NYU Langone Health, 2020). By contrast, if the
last of the glomeruli were changed, only about 5% would be
potentially dropped in the ability of the mouse to sense the
correct odor. (NYU Langone Health, 2020). 

21



 In order to identify what odors stand out within a mixture as
well, the right sensors must be activated in the correct order
and time. Any deviation in either of these abilities would
result in a decreased ability to accurately recognize and
categorize the smell. Following this transmission of electrical
signals to the glomeruli, they will proceed to the brain's cortex
(NYU Langone Health, 2020).

 Once the signal reaches the neurons of the cortex, the brain
takes further action. The piriform complex, a set of neurons
right behind the olfactory bulb, will work in attempts to
recognize the smell itself. 

   This complex is the only known structure other than the
hippocampus to have a three-layered allocortical structure. It
is activated when the pyramidal cell, a type of neuron,
receives information from the glomeruli and transmits it to
other brain regions (Vaughan, 2014). This also helps with
responses to specific odor mixtures by aiding in the formation
of a neural network that is capable of reliably transmitting
these messages.

    The anterior piriform complex is thought to hold information
on the molecular features of the odorant, whereas the
posterior piriform is for the odor's quality (Gottfried, 2006).
The piriform complex is additionally used to help differentiate
odors (Howard et al., 2009) and is involved with the working
memory, where odor information can be temporarily stored
(Zelano et al., 2009). In other words, it is crucial that this
complex is responsive and active to retain a highly
functioning smell identification and memory connection
system. It is from this complex that the information can then
be further passed over to other areas of the brain. 

   Having left off in our pathway at the piriform complex,
various cells within this structure will signal and move the
information to the thalamus, a complex key for translating the
neural impulses that come from the receptors to the cerebral
cortex. It is also essential for various sensorimotor
association functions, including motor activity, emotion, and
memory (Blumenfeld, 2018). From the thalamus, the
information can be passed to multiple locations, including the
hippocampus. This area is a vital part of the brain that stores
information involved with learning and memory and is a
crucial component of the olfactory system for this connection
to memory. When the neurons signal to the amygdala, the
portion of the brain involved with emotion, they can activate it
in ways that depend highly on the pleasantness of smell to
the individual (Zald & Pardo, 1997). The amygdala's location
helps make the association between memory and smell so
strong (Walsh, 2020). The amygdala portion of this process
contains a series of steps that refine the process. Since the
olfactory bulb also signals directly to the limbic system, it is
easy to register emotions in close coordination with the
smells encountered. Therefore, analyzing how the sense of
smell is associated with memory is very closely related to the
location of the centers in the brain that will respond. Since the
amygdala is so involved in the olfactory response,

 an expected response of emotional connection and memory
creation/retrieval is bound to occur. Just as some people
associate a particular smell with a bad memory, the brain
links various memories with the senses experienced,
resulting in these unfortunate retrievals. Similarly, we can
experience positive emotions with a particular smell, and both
of these examples would include many different interactions
of the brain to create the overall sensations we experience.
The combination of memory and smell is unique in many
ways for its strong connections with multiple critical areas of
the brain and the ability to recognize an abundance of smells.

 To smell an odor does much more than evoke a particular
memory, despite being an essential emotional contribution to
the human experience. It can create connections and
respond more substantially in the brain than previously
thought while contributing to brain function.

References

.1. Blumenfeld, H. (2018). Thalamus. Encyclopædia
Britannica. https://www.britannica.com/science/thalamus

2. Bushdid, C., Magnasco, M. O., Vosshall, L. B., &
Keller, A. (2014). Reports humans can discriminate more
than 1 trillion olfactory stimuli.
https://www.rockefeller.edu/research/uploads/www.rockefelle
r.edu/sites/8/2018/09/BushdidScience2014.pdf

3. Gottfried, J. A., Winston, J. S., & Dolan, R. J. (2006).
Dissociable codes of odor quality and odorant structure in
human piriform cortex. Neuron, 49(3), 467–479.
https://doi.org/10.1016/j.neuron.2006.01.007

4. Harvard Gazette.
https://news.harvard.edu/gazette/story/2020/02/how-scent-
emotion-and-memory-are-intertwined-and-exploited/

5. Howard JD, Plailly J, Grueschow M, Haynes J-D, Gottfried
JA. (2009). Odor quality coding and categorization in human
posterior piriform cortex. Nat Neurosci 12:932–8.
doi:10.1038/nn.2324

6. Malnic, B., Hirono, J., Sato, T., & Buck, L. B. (1999).
Combinatorial receptor codes for odors. Cell, 96(5), 713–723.
https://doi.org/10.1016/s0092-8674(00)80581-4

7. Manzini, I., Frasnelli, J., & Croy, I. (2014). Wie wir riechen
und was es für uns bedeutet : Grundlagen des Geruchssinns
[How we smell and what it means to us: basic principles of
the sense of smell]. HNO, 62(12), 846–852.
https://doi.org/10.1007/s00106-014-2925-2

8. Mayhew, Emily J., Arayata, Charles J., Gerkin, Richard C.,
Lee, Brian K., Magill, Jonathan M., Snyder, Lindsey L., Little,
Kelsie A., Yu, Chung Wen, Mainland, Joel D. (2022.).
Transport features predict if a molecule is odorous | PNAS.
https://www.pnas.org/doi/10.1073/pnas.2116576119

22Brain Matters・Volume V Issue ii

https://www.britannica.com/science/thalamus
https://www.rockefeller.edu/research/uploads/www.rockefeller.edu/sites/8/2018/09/BushdidScience2014.pdf
https://doi.org/10.1016/j.neuron.2006.01.007
https://news.harvard.edu/gazette/story/2020/02/how-scent-emotion-and-memory-are-intertwined-and-exploited/
https://doi.org/10.1016/s0092-8674(00)80581-4
https://doi.org/10.1007/s00106-014-2925-2
https://www.pnas.org/doi/10.1073/pnas.2116576119


9. NYU Langone Health / NYU School of Medicine. (2020,
June 18). Scientists decode how the brain senses smell.
ScienceDaily.
www.sciencedaily.com/releases/2020/06/200618150304.htm

10. Rinberg, D. (2020). Scientists decode how the Brain
Senses Smell. NYU Langone News.
https://nyulangone.org/news/scientists-decode-how-brain-
senses-smell

11. Vaughan, D. N., & Jackson, G. D. (2014). The
piriform cortex and human focal epilepsy. Frontiers.
https://www.frontiersin.org/articles/10.3389/fneur.2014.00259
/full

12. Walsh, C. (2020, February 27). How scent, emotion, and
memory are intertwined - and exploited. 

13. Zald, D. H., & Pardo, J. V. (1997). Emotion, olfaction, and
the human amygdala: amygdala activation during aversive
olfactory stimulation. Proceedings of the National Academy of
Sciences of the United States of America, 94(8), 4119–4124.
https://doi.org/10.1073/pnas.94.8.4119

14. Zelano C, Montag J, Khan R, Sobel N. (2009). A
specialized odor memory buffer in primary olfactory cortex.
PLoS One 4:e4969. doi:10.1371/journal.pone.0004965

23

http://www.sciencedaily.com/releases/2020/06/200618150304.htm
https://nyulangone.org/news/scientists-decode-how-brain-senses-smell
https://www.frontiersin.org/articles/10.3389/fneur.2014.00259/full
https://doi.org/10.1073/pnas.94.8.4119