Lecture 7: Chemical Senses

Question 1

Outline the neural pathway of olfaction.

Answer 1

Odorant –> Olfactory epithelium

—> olfactory receptor neurons (ORNs) which project, via olfactory nerve, to…

Olfactory bulb (glomeruli) where ORN synapse with mitral cells

mitral cell axons form the lateral olfactory tract that projects to Pyriform cortex

Question 2

Describe the pyriform cortex

Answer 2

Pyriform cortex

Primary cortical target of olfactory bulb/olfactory tract (in the temporal lobe)

“Archicortex”, meaning evolutionarily older than other parts of the cortex (3 layers rather than 6)

Pyriform cortex outputs (pyramidal cells) travel to the thalamus, which then projects to association cortex regions

Question 3

How is odorant perception in humans different than rats and dogs?

Answer 3

We have the least ORCs and therefore the worst sense of smell.

Question 4

What is the structure of the olfactory epithelium?

Answer 4

Olfactory Receptor Neurons (ORNs)

Receptor cells with olfactory cilia (not true cilia)

Contain chemoreceptors on cilia.

ORNs project through the cribriform plate to the olfactory bulb.

ORNs die after several days are continually replenished by basal cells, which are stem cells similar to those observed in the developing nervous systems.

Question 5

What is the function of the olfactory epithelium?

Answer 5

Cilia of ORNs detect odorants.

Effectively increase the surface area of the odorant-sensing region of the neuron, increasing sensitivity.

The olfactory cilia possess the chemoreceptors that produce the odorant receptor potential (this is a depolarizing potential, the figure above is showing the inward cation current).

Question 6

What is the structure and function of the odorant receptor of the ORN?

Answer 6

Actual odorant receptors are 7-transmembrane G protein-coupled receptors (Part of family that includes β-adrenergic receptors, muscarinic receptors & rhodopsin/opsin).

Although there are a large number of odorant receptor genes, but only a fraction are actually expressed.

Each receptor responds to a specific (& probably limited) set of odorants.

There appears to be a bilateral spatial arrangement of receptor expression.

Question 7

What is currently known about the neural distribution of distinct ORNs that pick up certain odorants?

Answer 7

In (A) and (B), green label is for olfactory marker protein (OMP) that labels all olfactory neurons. The red label in (A) is for adenylate cyclase III & is restricted to the olfactory cilia.

In (C) and (D) the green marker is for specific olfactory receptor types; note the distinct distribution.

Question 8

Describe the molecular mechanism for odorant transduction.

Answer 8

Odorant binds to receptor which activates a G-protein only found in olfactory receptor cells.

This activates adenylate cyclase III, which then activates a cyclic nucletide-gated channel.

The resulting Ca2+/Na+ influx depolarizes the cilia. This depolarization is boosted by a Cl- efflux mediated by a Ca2+-gated Cl-
channel.

The Na+/Ca2+ exchanger pumps Ca2+ out so that intracellular Ca2+ levels are returned to a level that does not activate the cyclic nucleotide gated channels.

The depolarization in the cilia propagates passively to the axon (see slide 4) where it initiates a Na +-mediated action potential the travels to the olfactory bulb.

Question 9

How do different ORNs respond to different odorants? (e.g. do they all respond the same?)

Answer 9

Even though we don’t know *why* the ORNs do what they do, we can clearly see a sort of labeled-line encoding.

Some neurons respond to one smell, others to a few smells, and then some respond to lots of smells.

Question 10

How is the olfactory bulb organized?

Answer 10

into glomeruli, which are balls of synapses between ORNs and mitral cells of the Olfactory Bulb

Note: 25,000 ORNs provide input in a glomeruli, while 25 mitral cells receive it.

Question 11

Describe the glomeruli in the olfactory bulb.

Answer 11

In the olfactory bulb are glomeruli, spherical structures where ORN axons form excitatory synaptic connections with dendrites from mitral cells (principal projection neurons).

Each glomeruli contains dendrites from ≈ 25 mitral cells and receives input from ≈ 25,000 ORNs.

Each glomeruli receives input from ORNs expressing the same single olfactory receptor.

Maximizes sensitivity, signal fidelity & signal/ noise ratio.

Glomeruli also contain dendrites from tufted cells and periglomerular cells.

Question 12

What is the role of granule cells in the olfactory bulb?

Answer 12

Granule cells make dendro-dendritic connections with mitral cells & form a lateral inhibitory network; contribute to both odorant processing and synaptic plasticity.

remember mitral cells are what synapse with the ORNs

Question 13

What is observed when we attempt to map responses of glomeruli to chemically-distinct odorants?

Answer 13

Odorants elicit a response in 1 or more characteristic glomeruli.

Increasing odorant concentration leads to increased level of glomeruli activation and increased number of activated glomeruli.

However, the response profile of glomeruli is not necessarily unique for an individual odorant.

Also, complex odors that have many separate components only activate a relatively small number of glomeruli that seem to represent key elements of a given odor.

So it’s unclear exactly how odorant identity is encoded

Part of the explanation may be that coding is sparse; little or no background activity and actual stimuli elicit only a few action potentials

There may be a temporal coding component on top of the spatial component.

Question 14

What three cranial nerves are involved with taste? What area do they innervate?

Answer 14

VII- Facial- anterior portion of the tongue

IX - posterior portion of the tongue

X- innervates epiglottis, gets some taste info

All 3 of these send their information to the medulla

Question 15

Taste cells synapse onto _____________ that project to the nucleus of the _________in the medulla.

Answer 15

primary afferents

solitary tract (NST)

Question 16

How is the NST involved in satiation?

Answer 16

(first, NST is getting information about taste)

The NST also receives visceral afferent input via the autonomic nervous system.

This represents a region in which chemosensory information is integrated with visceral input/output.

Involved in satiation/apetite response, insulin release.

Question 17

What reciprocal connections does the NST make?

Answer 17

There are also reciprocal
connections between NST with the
hypothalamus & amygdala (and
cortico-amygdala connections too).

Mediate subjective aspects of taste,
appetite, satiation, food-seeking
behavior.

Question 18

Fungiform papillae

Answer 18

highest density

contain 25% of the taste buds

only 2-3 taste buds per papilla

Question 19

Foliate papillae

Answer 19

only two bilateral pairs (posteriolateral surface)

contain 600 taste buds each (25%)

Question 20

circumvallate papillae

Answer 20

9, each with about 250 taste buds (50%)

Question 21

Taste buds are also present on what surfaces other than the tongue?

Answer 21

Soft palate, larynx, esophagus

total of 4000

Question 22

Name the 5 distinct categories of taste perception

Answer 22

salt

sweet

sour

bitter

umami

Question 23

Describe salt taste.

Answer 23

detection of dietary salts (e.g. NaCl)
and essential amino acids (needed for
protein synthesis)

Question 24

Describe sweet taste.

Answer 24

detection of sugars and other
carbohydrates (energy source)

Question 25

Describe sour taste

Answer 25

detection of acidity which can be
indicative of food palatability

Question 26

Describe bitter taste. (two examples, know)

Answer 26

detection of compounds that may
indicate a food item is poisonous
(e.g. quinine, strychnine)

Question 27

Describe umami taste.

Answer 27

savory (think Doritos); detection of
amino acids present in cooked
meats and other high-protein foods

Question 28

Describe the spatial distribution of taste buds on the tongue.

Answer 28

There is a differential spatial distribution of tastes bids sensitive to the 5 categories of
tastants, with sweet/salty/umami concentrated in the rostral tongue and bitter/sour in more
caudal areas.

Priority to assess nutrient content first and than palatability.
Sweet/salty/umami elicit salivation, mouth movements & swallowing behaviors, insulin release
plus pleasurable sensations.
Sour elicits larger salivary response to dilute out the offending taste and motor behaviors
(grimace, puckering) that discourage continual intake of the food item.
Bitter elicits protrusion of the tongue, gagging, spitting to prevent ingestion

Question 29

Name the thresholds for bitter, sour, salt, sweet, and umami tastants.

Answer 29

bitter tastants is quite low (8 μM quinine and 1 μM strychnine)

sour is much higher (2 mM for citric acid)

salt and sweet is even higher (10 mM NaCl and 20 mM sucrose)

umami is quite low (7 μM for glutamate

Question 30

Describe taste bud anatomy.

Answer 30

Taste buds consists of the taste pore, taste cells,
basal cells and axons from primary taste afferents.

The basal cells are stem cells that replace the taste cells when
 they degenerate (2 weeks).

The apical region of the taste cells have microvilli in
which the taste receptors are localized.

Tastant binding to the receptors produces a
depolarizing receptor potential that spreads to the
basal region of the cell where it elicits
neurotransmitter release onto primary sensory
afferents.

Question 31

What neurotransmitters are thought to be released by taste cells?

Answer 31

5HT and ATP

Question 32

What two types of receptor mechanisms do taste receptors utilize?

Answer 32

Some of the taste receptors are ion channels.
Others are G-protein coupled receptors that activate
ion channels.

Question 33

What is the receptor protein for salty things and how does it work?

Answer 33

amiloride-sensitive Na channel

Salt – simply Na+ influx through a voltageinsensitive
cation channel (amiloride
blocks ability to taste salt).

Question 34

What is the receptor protein for sour things and how does it work?

Answer 34

“H+ sensitive TRP channel”

Sour – appears to be mediated by a protonpermeant
TRP channel.

Question 35

What receptor subunit is shared by the sweet and umami taste cells?

Answer 35

T1R3

Both activate the same PLC–> IP3 –> TRPM channel pathway.

Question 36

T1R2 is the distinct subunit of what tastant receptor?

Answer 36

sweet!

(then PLC IP3 to TRPM channel pathway

Question 37

T1R1 is the distinct subunit of what tastant receptor?

Answer 37

umami (amino acids)

then PLC-IP3–> TRPM calcium channel opens.

Question 38

TRPM channels are part of what chemoreceptor pathway? What do they do?

Answer 38

taste reception

they allow Ca ion influx, activated by IP3.

Question 39

Describe the bitter tastant receptor protein.

Answer 39

Mediated by a single 7-transmembrane protein, T2R.

There are 30 T2R subtypes, each encoded by single gene, one of which mediates the ability to taste PTC.

Utilize same PLC–> IP3 –> TRPM channel pathway as sweet and umami

Question 40

Briefly describe the salt, sour, sweet, umami, and bitter taste transduction via ion channels and G-protein coupled receptors (picture).

Answer 40

view slide 16/19 in lecture 16

Question 41

How are different tastes distinguished?

Answer 41

If there is overlap in the sharing of signaling mechanisms, how are different tastes
distinguished?

Answer: Each taste cell expresses only one type of tastant receptor (see A on next slide).

This indicate a labeled-line coding for taste; a given taste elicits activity in a specific receptor
to CNS pathway. Segregation of specific taste pathways appears to be maintained all the
way to the insular cortex.

There is some degree of coding amount (concentration) and hedonic value by the number of action
potentials elicited in the primary afferents.

Question 42

Describe an experiment that demonstrated the labeled line coding of the taste system.

Answer 42

That labeled-line coding mediated taste was shown in experiments in which the TRPM
channel or PLC was genetically knocked-out.

In the TRPM KO animals, the capacity to perceive bitter, sweet and umami was eliminated.

In the PLC KO animals, PLC expression was selectively reinstated only in cells that express the T2R
receptor (bitter).

In those animals, the perception of bitter returned, but not the perception of sweet or umami.

This indicates that even though sweet, bitter & umami all share the same intracellular signaling pathway, the neural signals encoding these tastants are segregated at the receptor level and remain segregated all the way to the olfactory cortex.

Question 43

Graphically display how a TRPM knockout ould affect sweet, umami, and bitter taste. How would a T2R-rescue change this?

Answer 43

look up and study slide 18 of 19 in chemical senses lecture 16

seriously

Question 44

Why is trigeminal chemoreception important?

Answer 44

Detection of chemical irritants to the soft and mucousal-lined tissues of the head (nasal
cavity, scalp, cornea, oral cavity).

Question 45

What is the neuron type involved in the trigeminal chemoreceptive pathway ?

Answer 45

Is mediated by polymodal nociceptive neurons (similar to those that innervate the skin)
that project axons via the trigeminal nerve (CN V) to the trigeminal nucleus in the spinal
cord.

Question 46

Where do the axons involved in the trigeminal chemoreception pathway go? What do they do there?

Answer 46

Axons from the trigeminal nucleus project to the VPM of the thalamus and then to the
somatosensory cortex.

They elicit salivation, tearing, vasodilation, sweating, bronchial constriction.

Question 47

What potential irritants would trigger trigeminal chemoreception?

Answer 47

Potential irritants include sulfur dioxide, ammonia, methanol, acetic acid and capsaicin;
are detected at a higher concentration compared to the chemoreceptors involved in taste
and smell

Receptors mediating this chemoreception are not well known, but include the TRPV
receptors which probably detect acidic irritants. Other TRP channels are likely to be
receptors for other irritants.