2 Human Chemical Senses
Tom Finger
I. Introduction
A. Role of Chemical Senses in Behavior
B. Chemical Senses of humans
1. Smell
2. Taste
3. Chemesthesis: Trigeminal chemoreception
C. Clinical Complaints & how to distinguish between the chemical senses
D. Comparison of Chemical Senses
1. Receptor Cell & sensory endorgans
2. Cranial Nerve
3. Primary Sensory Nucleus in the Brain
4. Sensations & Utilization
II. Olfaction
A. Peripheral Anatomy
1. Orthonasal vs retronasal stimulation
2. Olfactory Epithelium
a. mucus layer & cilia
b. olfactory receptor neurons
B. Olfactory Transduction
1. G-protein coupled receptors
2. cAMP & cAMP-gated channels
C. Olfactory Bulb & Representation of Odors
1. Glomeruli: Odor Map
2. Output Cells: Mitral Cells
D. Central Olfactory Pathways
1. Olfactory Tract as tract of CNS
2. Piriform Cortex Orbitofrontal Cortex (Conscious appreciation of odor)
3. Entorhinal Cortex Hippocampus (Odor-evoked memories)
4. Olfactory Tubercle & Amygdala (Limbic/visceral responses to odors)
III. Taste
A. Taste qualities (bitter, sweet, salt, sour, “umami” [savory])
B. Peripheral Taste Apparatus
1. Distribution of Taste Buds: lingual vs extra-lingual
2. Lingual Papillae
3. Organization of Taste Buds
C. Diversity of Taste Transduction Mechanisms
1. ion channels (sour, salty)
2. second-messenger systems (bitter, sweet, umami)
D. Central Taste Pathways
1. nuc. solitary tract – orotopic map
2. VPMpc
3. taste cortex (in insular cortex)
4. “flavor” cortex = orbitofrontal cortex
IV. Chemesthesis: Trigeminal chemoreception
A. Free Nerve endings
B. Trp Channels (chemically-sensitive ion channels)
Fig. 1: The olfactory epithelium can be stimulated
either orthonasally, i.e. by odors entering the nostril, or
retronasally, i.e. by odors from substances in the mouth
which curve backward past the soft palate the enter the
nasal cavity from the rear.
Introduction
The ability to detect chemicals probably first evolved because of the necessity for
primitive organisms to detect sources of food and to avoid noxious compounds. However,
chemical cues provide not only information on the nature of the environment, but also serve as a
means of communication between organisms.
Traditionally the chemical senses are described as playing only a minor role in human
behaviors compared to other vertebrates. While it is certainly true that some species (e.g. dogs)
have a much more acute ability to detect smells, a close study of the chemical senses in humans
reveals that they are sophisticated systems that play important biological and social roles. The
sense of smell in humans can detect quantities of odorants in air that are below the detection
threshold of modern gas chromatographs. The parallel computation necessary for recognition of
most smells rivals that of the most sophisticated computers currently available.
Olfaction and taste are important clinically because they play a role in the regulation of
food intake, and contribute greatly to our quality of life, including perhaps a subconscious role in
our selection of partners. A sudden loss of smell (anosmia) or taste (ageusia) can be
devastating, particularly if the individual depends on smell for their trade or occupation (for
example for cooks and perfumers), and can often lead to severe depression. Olfactory input to
our brain can cause strong reactions. All of us have probably experienced vivid memories
evoked by a familiar odor; baking bread and the memory of one’s grandmother for example.
Other, less poetic facts underscore the special power of chemosensory input on the brain. The
association of particular foods with subsequent nausea leads to long-lasting avoidance of that
food. These acquired food aversions can be of clinical importance. For example, patients
undergoing chemotherapy frequently develop an aversion to some foods because they associate
each meal with the nausea they feel due to the treatment. So, many physicians suggest that
patients try new foods during the time of chemotherapy so the patients develop aversions to food
they don’t normally eat and therefore can resume
a normal diet after the end of treatment.
Chemosensory systems used by humans.
The colloquial use of the term “taste” is
imprecise, and in fact, what is usually called a
“taste” sensation involves stimulation of three
sensory systems: olfaction (smell), gustation
(taste proper) and chemesthesis (detection of
irritant chemicals by trigeminal nerve endings).
The sense of taste utilizes taste buds present in
the oral cavity (tongue and palate) to detect
sweet, sour, salty, bitter, and the taste of
monosodium glutamate (umami, see below).
Olfaction utilizes olfactory receptor neurons
located in the neuroepithelium lining the roof of
the nasal cavity to detect and identify thousands
of smells or flavors delivered into the nose either
through the nostrils, or, in the case of flavors in
foods, retronasally (see Figure 1). Finally, chemesthesis utilizes chemosensory receptors
localized in the sensory processes that trigeminal neurons extend into the nasal and buccal
cavities to detect irritant or noxious stimuli (e.g. capsaicin — the main irritant component of chili
peppers, CO 2 in carbonated beverages, mints, mustard or vinegar [acetic acid]). Activation of the
chemesthetic system usual provokes protective reflexes such as gagging, choking, coughing or
local tissue inflammation.
It is important to take into account the common confusion of the terms taste and smell
while evaluating patients complaining of a chemosensory deficit. Approximately 2/3 of patients
who come to a chemosensory clinic complain of a taste loss. Nevertheless, most of these patients
are found to have smell dysfunction while fewer than 10 % have a measurable gustatory deficit.
Accordingly it is important for you to learn how to distinguish deficits in taste from deficits in
olfaction since diagnosis and treatment will vary substantially according to the system involved.
Note: A fourth chemosensory system whose receptors lie in the nasal cavity of many
terrestrial vertebrates (but not humans or old-world primates) is the vomeronasal system. This is
a system that detects pheromones, which are chemical signals that communicate social and
sexual information. In human embryos a vomeronasal organ is present but degenerates during
mid-late gestational stages. In many adults, a remnant “vomeronasal pit” can be detected
ventrally in the anterior part of the nasal cavity. However, despite what many magazines,
tabloids and late-night infomercials would have us believe, this vomeronasal pit does not appear
to function as a chemosensory organ in adults. Humans do detect pheromones and other
conspecific chemical signals, but do so via the main olfactory epithelium.
TABLE I: COMPARISON OF CHEMICAL SENSES
SMELL TASTE CHEMESTHESIS
Receptor Cell Ciliated, bipolar neuron Modified epithelial cell
(Synapses onto nerve fiber
from cranial ganglion cell)
Free Nerve Ending of
Cranial Ganglion Cell
Cranial Nerve CN I CN VII, IX, X CN V (mostly)
Primary Sensory
Nucleus in CNS Olfactory Bulb Nuc. of the Solitary Tract Spinal Trigeminal
Nucleus
Morphology of
Sensory
Epithelium
CN I
Taste
Receptor
Cell
Nerve Fiber
CN VII, IX or X
Taste Pore
synapse
Free Nerve Ending
Nerve Fiber
CN V
OLFACTION
The chemical structure of odorant molecules is what determines the olfactory quality of
each compound. The main task of the peripheral olfactory system is to inform the brain (via the
olfactory bulb) of the quantity and odorous quality of the volatile chemicals that enter the nose.
Peripheral Anatomy of the Olfactory System
Fig. 1 shows the location of the olfactory neuroepithelium in the human nasal cavity and
Table 1 shows its morphology. The olfactory neuroepithelium is covered with a thin layer of
mucus. Olfactory neurons (also called olfactory receptor cells) extend thin processes (cilia) into
this mucus layer. Because the cilia are very long (5-20 m, with a diameter of 0.1-0.25 m), the
area of the membrane of the olfactory neuron that is exposed to the mucus is much larger than it
would be if the cells did not possess cilia. On this vastly expanded surface area of ciliary plasma
membrane odorants dissolved in mucus interact with olfactory receptor proteins. In addition,
most of the biochemical machinery necessary to convert chemical information into electrical
information is located at the olfactory cilia. Notice that the olfactory neurons are bipolar neurons
(i.e. a dendrite at one end [apically] and an axon emitted from the other end [basally]) and that
they send a single, very thin (0.2 m in diameter) unmyelinated axon towards the olfactory bulb
as part of the olfactory nerve (CN I).
Since the olfactory neurons are exposed to the external environment, they are subject to
attack by bacteria, viruses and environmental toxins. Perhaps because of this, olfactory neurons
are the only neurons that are continuously undergoing replacement by neurogenic basal cells.
Thus the olfactory receptor cells you are using today are entirely different than the ones you used
a month ago. Basal cells that lie underneath the epithelium serve as precursors for the generation
of new olfactory receptor neurons. The property of turnover of the receptor cells makes this
system vulnerable to systemically applied mitotic disruptors used in treatment of cancer.
Peripheral mechanisms of olfactory transduction
The initial recognition of odors occurs via olfactory receptor proteins located on the
membrane of the olfactory cilia. The 2004 Nobel Prize in Medicine was awarded to Buck and
Axel (Columbia University) for cloning a large multi-gene family of olfactory receptors. It is
estimated that humans have a few hundred functional olfactory receptor genes; dogs have over
1000. The olfactory receptor proteins possess seven transmembrane spanning regions and
resemble other G-protein coupled receptors such as those that respond to some neurotransmitters
and hormones (such as serotonin and epinephrine). Each mature olfactory receptor neuron
expresses one olfactory receptor protein. Note however that each olfactory receptor protein may
bind numerous different odorous compounds when the different compounds share a common
chemical structural feature. Conversely, a particular odorant is likely to engage a variety of
odorant receptors with each recognizing a different structural domain on the odorant. This is
analogous to the way the adaptive immune system operates.
In order for information to be transmitted to the olfactory bulb, the receptor neuron must
generate an action potential. This is accomplished through a biochemical cascade, which
amplifies the transduction event way out in the cilia to ultimately cause sufficient depolarization
of the cell body that the cell reaches threshold for generation of an action potential. When an
odorant binds to the receptor protein, the associated G-protein (G olf ) activates adenylate cyclase,
which locally generates cAMP. The cAMP opens a nearby cAMP-gated ion channel permitting
influx of Na + and Ca 2+ . The local increase in Ca 2+ opens adjacent Ca 2+ -gated Chloride channels.
Since Cl – levels in the receptor cell are quite high, opening a Cl – channel results in outflow of Cl –
thereby further depolarizing the cell. This amplified depolarization is sufficient to drive the cell
to threshold thereby triggering an action potential.
Just as taste receptor molecules are expressed by diverse organ systems of the body,
olfactory receptor proteins also serve as chemoreceptors outside of the olfactory system.
Examples of tissues exhibiting functional olfactory receptors include kidney and lung. In each
situation, the olfactory receptor proteins detect particular substances, but the downstream effects
on cellular function vary according to each system.
Olfactory Bulb
In order to evoke the perception of an odor, the signals coming from the olfactory
neurons must be processed in the olfactory bulb and higher projection areas of the central
olfactory system. Axons of the olfactory neurons penetrate the ethmoid bone (cribriform plate)
and converge on glomeruli, which are spherical neuropil structures (a tangle of axons and
dendrites) present at the outer layer of the olfactory bulb. In each of these glomeruli,
approximately 1000 axons (each from a single olfactory neuron) make excitatory synaptic
connections with the apical dendrite of 2-25 mitral (or tufted) cells (Fig. 2).
Fig. 2: ORNs expressing the same odor receptor protein (red or blue) project to the same
glomerulus. Thus the odor world is mapped onto the olfactory bulb according to odor quality.
From Mori et al., Science 1999
Olfactory receptor neurons expressing the same olfactory receptor protein project their
axons to the same glomerulus. This convergence of axons that stem from receptor neurons with
the same chemical specificity has been postulated to be the basis for the ability of the olfactory
system to recognize among structurally dissimilar odorants. Thus the primary principle of
encoding odor quality is through a odor-related map of glomeruli in the olfactory bulb. In
contrast, within the olfactory epithelium, receptor cells expressing a common receptor are
scattered throughout the epithelium.
When a subject is stimulated with a pure olfactory compound and the response of the
olfactory bulb is recorded, many glomeruli respond to each individual odorant. As a result, it
appears that each odorant can stimulate a number of receptors. The response to single odorants is
usually not localized to a single glomerulus but is distributed in wide areas of the glomerular
layer. Therefore, identification of an odor entails recognition of the pattern of activity across all
glomeruli of the olfactory bulb.
Central olfactory pathways (Fig. 3)
The olfactory system is unique among the senses since the output of the olfactory bulb
projects directly to the cortex. All other senses project to cortical areas indirectly through a relay
at the thalamus. The axons of output cells from the bulb collect into the lateral olfactory tract.
These axons project directly into olfactory cortex and a portion of the amygdala. The olfactory
cortex consists of the lateral olfactory gyrus and part of the uncus. Olfactory cortex is divided
into several areas including the piriform cortex, the accessory olfactory nucleus and the olfactory
tubercle. The piriform cortex projects to the orbitofrontal cortex, both directly and via MD
nucleus of the thalamus. Orbitofrontal cortex is an association area for olfactory and taste
information, and it is thought that this pathway results in our conscious appreciation of smell (see
above). The other major connections are associated with elements of the limbic system: the
amygdala, olfactory tubercle and entorhinal cortex. Amygdala and olfactory tubercle are
interconnected with the hypothalamus, which is intimately involved in the subconscious
regulation of homeostasis, circadian, reproductive and other biological activity patterns. The
entorhinal cortex feeds into the hippocampus. which is a major player in the storage and retrieval
of memories.
Fig. 3: Schematic Diagram of Central Projections of the Olfactory Bulb and Functional Role of each
secondary olfactory target.
Olfactory
Bulb
Entorhinal Cortex
Hippocampus
Memories
Piriform Cortex
MD Thalamus
Orbitofrontal Cortex
Conscious
perception
Olfactory
Tubercle Amygdala
Hypothalamus
Visceral
reactions;
homeostasis
Olfactory Tract
http://www.juniordentist.com/list-of-papillae-of-
tongue-location-and-histology.html
Figure 4: Location of different papillae on
the tongue. Fungiform, vallate and foliate
papillae house taste buds; filiform do not.
TASTE
The sense of taste provides information to the brain on the chemical composition of food.
Most chemicals that stimulate taste cells are water-soluble. Taste informs us about the salt
content of the diet (salt taste), the presence of high-energy carbohydrates (sweet) or proteins
(umami), and the pH (sour). In addition, bitter reports the presence of potential toxins. The taste
quality called umami, which means “savory” in Japanese, signals nutritive material of organic
origin, e.g. glutamate. Innately (i.e. as infants), we reject sour or bitter substances and ingest
sweet, “umami” or mildly salty ones. The bitter taste of some medications can be the limiting
factor in getting a patient to take the proper dosage.
Organization & Innervation of the peripheral taste system
Taste receptor cells are not uniformly
distributed over the surface of the tongue and
oropharynx, but rather occur in discrete ovoid
structures called taste buds mostly situated within
taste papillae (Fig. 4). The majority of taste buds in
humans are on the tongue, but we also have
numerous taste buds on the soft palate, oropharynx,
and epiglottis. The posterior taste buds are more
involved in consummatory reflexes, (e.g.
swallowing, choking) than with conscious
appreciation of taste quality.
Lingual taste buds lie on specialized bumps
or grooves, called taste papillae (Fig. 4). The three
kinds of taste papillae are classified according to
their shape and number of taste buds: fungiform
papillae are located all over the anterior end of the
tongue, foliate papillae on the sides, and
circumvallate papillae at the posterior part of the
tongue. Stimulation of a single taste papilla can be
sufficient to identify the taste quality of the stimulus.
Filiform papillae are non-taste papillae and serve as tactile organs.
The chorda tympani branch of the facial nerve innervates fungiform taste papillae in the
anterior 2/3 of the tongue, while the glossopharyngeal nerve innervates the circumvallate
papillae. Taste buds located in the soft palate are innervated by the superior petrosal branch of
the facial nerve, and the taste buds in the extreme posterior tongue, oropharynx and epiglottis are
supplied by the vagus. Taste buds in these posterior areas are thought to be important in gag
reflexes designed to stop intake of spoiled foods or noxious compounds.
Morphology of the taste bud
In mammals each taste bud consists of approximately 50-100 cells (Fig. 5). Of the three
types of elongate cells in the taste bud only some express taste receptor proteins; others are more
like glia. Each cell in a taste bud has a limited lifespan (10-30 days) and is replaced from
proliferative basal cells situated at the bottom and along the edge of the taste bud (see Fig. 5).
The basal cells serve as the stem cells from which the other cells differentiate. Taste cells make
functional contact with gustatory nerve fibers from the facial (VIIth), glossopharyngeal (IX) or
vagal (X) cranial nerve depending on location in the oral cavity and oropharynx (see above).
Depolarization of taste
cells leads to release of
transmitter from the basal
portion of the cell. In the taste
system ATP (acting on neural
P2X3 receptors) is crucial in
transmission of taste
information. Drugs that block
P2X3 receptors (to relieve pain)
can cause loss of taste, which
can limit patient compliance
with these treatments.
Individual afferent
neurons contact a number of
taste buds, and within each taste
bud each fiber innervates a few
receptor cells. The individual
taste receptor cells respond
mostly to one class of taste
stimuli, e.g. bitter or sweet.
Electrical recordings from taste
nerves show that most single
fibers predominantly signal the
presence of a particular taste quality, while other fibers are more broadly tuned e.g. to ionic
stimuli. Apparently, the central nervous system extracts information from the population of
afferent fibers activated by a particular chemical stimulus on the tongue to determine its sensory
characteristics. This is analogous to color vision where the brain can determine the color of a
stimulus only by comparing inputs from 3 different color cones.
Transduction Mechanisms for Taste
As mentioned above, the taste system detects a diverse array of molecules and to do so
must utilize a host of different mechanisms. Some stimuli, e.g. salts or protons, can permeate ion
channels directly to depolarize the receptor cell. Other taste substances, e.g. sugars, bitter and
glutamate rely on metabotropic (G- protein-linked) receptors. Of the 30 or so human taste
receptor genes identified to date, 27 encode bitter receptors and only 3 are involved in detection
of sweet or umami. Individual differences in primary structure of the receptor proteins
(polymorphisms) can lead to different degrees of sensitivity to particular taste substances. The
most common example is differential sensitivity to PROP (Propylthiouracil). Such differences in
sensitivity may affect both diet and tolerance for bitter-tasting medicines. People with high
sensitivity to bitter substances tend to eat fewer vegetables (e.g. broccoli is a bitter vegetable)
and tend to have higher incidences of nutrition-related disease, e.g. colonic neoplasms (Basson et
al., 2005).
Even more curious is that taste receptors are expressed by many cells of the body
including epithelial cells of the airways, e.g. in nasal cavity, trachea and bronchi. The cells in
these areas use the so-called “bitter” taste receptors to detect and respond to bacterial signaling
molecules. When the airway epithelial cells detect the presence of large populations of bacteria,
the epithelial cells mount a local defense and also alert elements of the innate immune system.
Some papers report that the same taste receptor is used to detect PROP and bacterial signal
molecules. As a result, people who are unable to detect PROP may have a higher incidence of
Figure 5: Organization of a Taste Bud. Gustatory fibers enter the
taste bud (intragemmal fibers) whereas most somatosensory fibers
innervate the surrounding epithelium (Perigemmal Fibers).
Tastants dissolved in saliva reach the elongate receptor cells
through the taste pore, which is a small opening in the epithelium.
Taste receptor cells synapse onto the intragemmal fibers.
Proliferative basal cells generate new taste cells just as they
generate new cells in the surrounding epithelium.
respiratory bacterial diseases (Lee et al J Clin Invest. 2012.) apparently because they are
deficient at detecting and responding to the airway bacteria. Other investigators fail to replicate
this finding.
Central Taste Pathways (Fig. 6 & 7)
Primary afferents from the tongue run in the facial (VII), glossopharyngeal (IX) and
vagus (X) nerves. When these axons enter the CNS they synapse on second order neurons in the
rostral area of the ipsilateral nucleus of the solitary tract (NST) [see Fig. 7]. The NST is
organized “orotopically”, i.e. there is a map of the oral cavity in the nucleus so that anterior parts
of the mouth are represented anteriorly in the nucleus.
Figure 6: Central Taste Pathways – Connections to hypothalamus & amygdala are related to control of
food intake; conscious appreciation of taste is mediated by cortex.
Taste Lemniscus: Second order cells (in
rostral portions of NST) send axons bilaterally
to the medial part of the ventrobasal thalamus
(VPMpc: see Fig. 6). The thalamic neurons
then send their axons into the anterior insular
cortex. Because the information ascends
bilaterally, a stroke involving insular cortex of
one side results only in decreased taste
sensitivity, but not unilateral loss (Pritchard,
Behav Neurosci. 1999 Aug;113(4):663-71).
Secondary gustatory cortex, located in the
orbitofrontal surface, can be considered flavor
cortex since it receives projections from both
primary gustatory cortex as well as from
olfactory areas. The orbitofrontal cortex is
presumably where integration taste and smell
leads to the perception of flavor.
Sub-conscious pathways for taste information: The NST also relays taste information to
the hypothalamus and amygdala for regulation of food intake and for visceral reactions to
ingested foods. Also the NST has reflex connections to nuclei in the brainstem involved in
Taste Bud
Nucleus of
the
Solitary Tract
VPMpc
CN VII, IX or X
x)
Taste
Cortex
(insula) Bilateral to
thalamus &
cortex
Bilateral to
Hypothalamus
& amygdala
Mucus
layer
Reflex connections to: salivatory
nuclei, nuc. ambiguus,
hypoglossal nuc., and medullary
reticular formation
For conscious
appreciation of taste
For sub-conscious
reactions to taste&
control of appetite,
etc.
Fig. 7: Cross-section of the brainstem through the
rostral medulla showing the rostral part of the
nuc. of the solitary tract where taste input relays.
gagging (nuc. ambiguus), swallowing (e.g. nuc. ambiguus, hypoglossal nuc.) and salivation (sup.
& inf. Salivatory nuc.).
Chemesthesis: Trigeminal chemoreception
Chemesthesis is defined as chemical sensitivity of mucous membranes and skin. A
number of substances activate free nerve endings situated just below the surface of the
epithelium. In cornified epithelium, these nerve endings lie mostly in the dermis and hence are
not accessible to most chemical agents. In contrast, nerve endings in mucous membranes can
approach to within a few micra of the surface, reaching to just below the line of tight junctions.
Thus many lipid-soluble agents can penetrate the epithelial barrier to reach the nerve endigns.
Examples of such chemicals include mints, capsaicin (hot-pepper extract), pipperine (from black
pepper), mustard oil and principals in many spices such as cinnamon, cloves and oregano.
Activation of free nerve endings by these common food ingredients gives rise to a tingly, cool or
hot sensation used to advantage by many chefs and cuisines to add to a flavor profile of food.
These compounds activate the nerve endings directly by gating a family of ion channels called
Trp channels (transient receptor potential). Different sensitivity nerve fibers have different
channels and hence respond to different chemicals. For example, cool/cold fibers have a
menthol receptor (TrpM8) while hot-fibers have the capsaicin receptor (TrpV1) and mustard oil
receptor (TrpA1).
Summary of Taste Cell Types and Functions
The version of this in your Course Packet (bottom half pg. 100) is incorrect. Please cross it
out or make a copy of this and paste over it.
EXTRA EXTRA Special COVID-19 Edition EXTRA EXTRA
The advent of Covid-19 has brought new attention and focus on the senses of taste and
smell. One of the key (CDC-recognized) symptoms of Covid-19 is a sudden loss of smell and/or
“taste”. A patient may be fine one day, and despite clear nasal passageways, be completely
unable to smell anything the next day. Some recent studies estimate that upwards of 70-80% of
Covid patients report loss of smell or taste with almost 50% of patients reporting this loss as the
first symptom (other symptoms include fever, headache, dry cough).
Unfortunately, much of the popular press and facebook coverage of this sensory loss do
not do a good job of distinguishing between smell, taste and flavor. Careful analysis of the
clinical and patient reports show that both taste and smell are affected by the disease, but to very
different extents. Taste loss (as defined by answers to questions regarding detection of salt and
sugar) does occasionally occur as an early symptom but rarely lasts more than a few days. In
contrast, the loss of olfactory capabilities – for both ortho- and retronasal function – can last
much longer, with some patients showing a continued olfactory dysfunction for longer than 1
year. Patients often describe this as a loss of taste and smell, but more detailed questioning
usually reveals that taste function (e.g. sweet vs salty) is intact, but perception of flavor (via
retronasal olfaction) is lost along with orthonasal olfaction. Further, the olfactory loss often
transforms over a period of weeks to months into a dysosmia, including phantom smells and
persistent malodors (parosmia).
The big difference in time-course and degree of loss for taste and olfaction suggests a
difference in mechanism of loss. Since the binding site for SARS-CoV2 is known, ACE2,
scientists can identify those cells that are directly impacted by the virus. Given the symptoms, it
is surprising that olfactory receptor neurons do not express ACE2 and therefore are not direct
targets of the virus. Rather, the surrounding supporting cells have the ACE2 receptor and
therefore the virus attacks those cells. The supporting cells, then respond to virus attack by
changing transcriptional profile to generate anti-viral agents. In so doing, they no longer support
the receptor cells, which fail to function properly. Once the virus clears, the supporting cells and
receptor cells return to normal function. This explains short term olfactory loss.
But some patients experience long term loss lasting months or years; what is happening
to them? In these cases, the virus kills the supporting cells and the loss of those cells causes a
secondary loss of the receptor neurons resulting in anosmia. Proliferation of the epithelial basal
cells can regenerate new receptor neurons over a period of several weeks or longer, but that is
unsuccessful in many patients and may result in mis-wiring of the new receptor neurons resulting
in parosmias.
Glossary
Ageusia – loss of sense of taste
Dysgeusia – altered perception of taste (often persistent bad taste)
Anosmia – loss of sense of smell
Hyposmia – diminished sense of smell
Dysosmia – altered or distorted sense of smell
Parosmia – Altered perception of smell in the presence of an odor, usually unpleasant
Phantosmia – Perception of smell without an odor present
_________________
Learning Objectives: (most important in BOLD)
1. Describe some simple tests you can do in a clinical setting that will enable you to
distinguish a deficit of olfaction from a deficit of taste. Know the clinical terms for
losses of these senses (e.g. ageusia = loss of taste; anosmia = loss of smell) or
dysfunctions of these systems (dysosmia = dysfunction of smell; dysgeusia =
dysfunction of taste).
2. Describe the differences in morphology and functioning of receptor cells for taste,
trigeminal (chemesthetic) and olfactory modalities.
3. Describe the difference in route of access of odorants to the olfactory epithelium during
orthonasal and retronasal stimulation.
4. List the three types of lingual gustatory papillae and indicate which cranial nerve
provides their gustatory and general cutaneous innervation to each area of the tongue.
5. Name the primary sensory nucleus for taste in the brainstem and give the location of
primary gustatory cortex.
6. Describe the way odor information is transmitted from the receptor epithelium to the
olfactory bulb. Compare how an odor is represented within the receptor sheet and within
the bulb.
7. List the output pathways and targets of the olfactory bulb. What behaviors or cognitive
events are associated with each of the olfactory target areas of the telencephalon?
Study questions.
1. Contrast the neural pathways for taste and smell. What is the presumed neural correlate for
the peculiar ability of odors to evoke emotional memories? How are odors represented in
the olfactory bulb?
2. What are the mechanisms of taste and olfactory transduction?
3. How can you tell the difference between taste, smell and trigeminal chemoreception in a
clinical setting? How can you determine which modality is affected by a dysfunction
or illness?