14 Olfaction 2012-1

-receptor cells are neurons
-long distance
-chemesthesis refers to ability to detect irritating stimuli
-vomeronasal requires contact w/stimuli; important for mammals, but
not for primates Chemoreception

Nasal Oral
Chemoreception Chemoreception
(Smell) (Taste)

Olfaction Chemesthesis Gustation Chemesthesis
(Trigeminal Chemoreception) (Trigeminal Chemoreception)

Vomeronasal
Chemoreception

Introductory Neurobiology 2012

Olfaction,
The Common Chemical Sense and
Vomeronasal Chemoreception


-nasal cavity is where we
sense odors
-two routes: sniffing
directly through the nose or
through the nasal cavity


Chemosensory
Systems
in Mammalian
Nose:

•Main Olfactory
-general odorants

•Accessory Olfactory
(Vomeronasal)
-pheromones

•Trigeminal
(Chemisthesis)
-irritating/pungent
volatiles
Rodriguez. Nat. Neuro.(2003)

-pheromones are instinctual, but
not entirely
-detecting predators, aggressive
displays, maternal behavior,
finding mates, provides direct
input to amygdala


Olfaction (Smell)
-hyposmia: reduced sense of smell
-anosmia: no sense of smell; can have a general
or specific (lose ability to smell specific odors)
-cacosmia: having olfactory hallucinations
[smelling things that aren't there]


The Importance of Olfaction


Our Sense of Smell
Can really influence and alter our
mood
Can influence how long we stay in a
room
Sharpens our awareness of other
people places and things.
Can influence who we talk to and
who we want to talk again (if
histocompatability group is different,
better chance of bonding)

Early warning system


“The Dogtor is in”
(Pet Scans)
-sense odor from body

Moles-melanoma
Breast cancer
Lung cancer


Specificity and intensity of dog
responses to breath/urine

99% accurate vs biopsies!


Flavorretronasal smell
-majority of flavor is smell, predominantly
-olfactory bulb in human is less than size of pinky nail

Bitter
Sweet
Sour
Salty
Umami
(MSG)


Emotions Memories

-olfactory memories are very strong
-Several branches of olfactory nerve going to olfactory bulb
-olfactory bulb provides direct input to the amygdala; also
involves memory

Odor and Memories

Recall
Vision: 50% accurate after only 3
months
Smell: 65% accurate after a year


Structure of the Nose


-crib inform plate separates nasal cavity from brain; olfactory nerves
terminate in olfactory epithelium
-receptor cells are neurons
-first synapse is in the brain; in olfactory bulb
-neurons terminate in cilia

The Olfactory Epithelium
The nose is the gateway to the brain
(problem if wacked in nose, can get brain
infections; diseases by amebas get into
nerve and go to brain)
Potential risks of trauma to the nose


-cilia is where initial events in
sensory transduction take place

Linda Buck

-plate is very thin bone
-neurons can regenerate, but there is a lot of scar tissue that can prevent neurons
from going back to place


-first synapse is in olfactory bulb
-neurons will go to glomerulus
-there is a specificity in glomeruli


-pathway is from OE to OB
to OC
-sense of smell goes
through cortex then the
thalamus
Linda Buck

Transduction
Mechanisms
in Mammalian
Nose
-g-protein is Golf
-cAMP will open ion
channel that allows Na
and Ca to come in
-Ca will open Cl
channel to leave neuron
to further depolarize
-same tranduction
pathways for smells,
difference in receptor
-~300 different
receptors
Rodriguez. Nat. Neuro.(2003)

The Olfactory Receptor Neuron


From: S. Ramon y Cajal y
J.F. Tello y Muñoz. 1931


-when we stimulate neuron,
we generate receptor
potential
-if receptor potential is
sufficient, it will generate
AP


How many different odors can
Humans discriminate?

A.~ 300
B.~ 1, 000
C.~ 10, 000
D.~ 1 million

Common Odors


Mechanisms of
Olfactory Transduction


-each olfactory receptor expresses only one of the receptors


Olfactory Coding

Glomeruli


-there is coding by
glomeruli
-all same receptor cells send
their axons to the same
glomeruli
-individual receptors tend to
go to individual glomeruli


-receptor 1 responds to
moer than one odor but
respond to differnt intensity
-coding is combination of
labeled-line and cross fiber
coding


Olfactory Receptor Genes
• Approximately 1000 genes in rodents
• Each olfactory receptor neuron expresses
only 1 olfactory receptor
• These same receptors are expressed in the
testis on sperm cells


Nobel Prize in Physiology or Medicine 2004
Protein must be able to
detect a large number of
odorants
One gene, multiple
combinations (like
immunity)
A large family of genes
each encoding a different
receptor

RICHARD AXEL LINDA BUCK Discovered the Odorant
Receptor Gene family (in
1991)

HUGE gene family Receptor
Odorant Genes
Large fraction of our genome
Scattered throughout all of our
chromosomes
Each odorant gene codes for a
protein that is sensitive to a
particular chemical structure(s)
• combinattion of receptors
(1625)


-how single glomerulus
receives axons from
neurons expressing one
receptor
-one receptor one
glomerulus


-similar receptors are not distributed
randomly, located in zones
-specificity of zonation for olfactory
receptor neurons


Introductory Neurobiology 2012 Linda Buck

-olfactory epithelium is like a mosaic of different
receptor neurons expressing different individual
receptors

Linda Buck

Mori K. et al. Science (1999)

* ~ 1000 OR types
* One OR type per cell
* Subset of OR types per zone
* Zone to Zone projection
* Cells of the same type project to a small number of fields (glomeruli)
* Different odors activate different fields

-shows convergence

Linda Buck

-shows zone in olfactory
epithelium and axons
projecting to different
glomeruli

Linda Buck

-4 receptor and
odorants
-multitude of
combinations are
possible
-w/300 different
receptors and 1000
different odors

Linda Buck

-combinatorial coding is superimpozed on zonal label line coding

Linda Buck

The Common Chemical Sense
(Chemisthesis)

The importance of the common
chemical sense


(Chemisthesis)

Receptors


-receptors for CCS are neurons; primary
sensory neurons
-form synapses in spinal cord


-trigeminal nerve is the fifth
cranial nerve
-burning sensation


(Chemisthesis)

Mechanism of transduction:
Activation of TRP channels


Trigeminal Chemoreception
TRP channels are located
directly on trigeminal nerve

Heat measured in Scovill units


Capsaicin desensitization

Trigeminal Ganglion Peripheral Nerve

Peripheral Terminal

To Brain Stem

Eye,
Nose,
-if acute stimulation, nerveACUTE TREATMENT or Mouth

is stimulted
-if chronic, nerve will
become desensitized
-if neonateal, nerve can be
killed and not recover CHRONIC TREATMENT
vanillyl aclyamide alkyl chain

NEONATAL Neurobiology 2012
Introductory TREATMENT

Figure 3 VR1 responds
to purified vanilloids and
pepper extracts.. c,
Responses to capsaicin
(10 M) and extracts
derived from four
varieties of peppers in
oocytes expressing VR1
(30 s application).
Bottom right, relative
potencies of each pepper
extract are plotted (mean
s.e.m., n = 3). Values
were normalized in each
cell to responses obtained
with capsaicin (10 M).
Extracts evoked no
responses in water-
injected cells. Reported
pungencies for pepper
varieties (in Scoville
units) are: Habanero (H),
100,000–300,000; Thai
green (T), 50,000–
100,000; wax (W),
5,000–10,000; and
Poblano verde (P), 1,000–
1,500 (ref. 23). Capsaicin
(C) is rated as
16x106 units.

From Caterina et al., Nature 389, 816 - 824 (23 Oct 1997)

Relative “burn” of some
common peppers

• Bell pepper 0
• Jalapeño 2,000 - 5,000 units
• Serrano 5,000 - 15,000 units
• Thai 50,000 - 100,000 units
• Habañero 100,000 - 300,000 units
• Ghost pepper 1-3 million units!!!

Vanilloid receptor 1 (VR1)
(TRPV1)
Vanilloid-like receptor 1
(VRL-1)(TRPV2)


-ligand-gated
channel
-capsaicin is fat-
soluble
-makes receptor
open up at room
temperature


Cool Receptors
(TRPM8)


-TRPM8
responds to cold
and menthol


TRPA1

• Mustard oil
∀ ∆9-tetrahydrocannibinol
• Cinnamaldehyde


Stimulation of Nasal
Trigeminal Fibers
• Associated with painful or irritating chemicals
(tingling, stinging, burning)
• Examples of physiological reflexes
– decreased respiration
– increased nasal secretion
– closure of nares and glottis
– sneezing
• Effects of noxious stimulus is minimized and the
individual is protected from further exposure


Vomeronasal Chemoreception
and Pheromones


Pheromones
Definition: any chemical or set of
chemicals produced by a living
organism that transmits a message to
other members of the same species.
Naive response, not learned
e.g. pups suckle, males fight, and estrus
cycles are altered.
Their precise nature remains
somewhat controversial
• males have more whisker growth


Invertebrate Pheromones

First discovered in
silkworm moths
Females secrete a
specific blend of
odorants that is highly
attractive to males
males fly upwind to
find the source (as far
away as a mile away)

Vertebrate Pheromones

Swabbed Hamster
A male hamster swabbed with hamster
pheromone (“Aphrodisin”) became sexually
attractive to another male hamster


Bruce Effect

Male Urine can induce
estrus (heat)
Bruce effect = odor
memory
Same mouse: pregnancy
maintained
New mouse or urine spike
with pheromone:
pregnancy terminated

The Importance of the
Vomeronasal Organ (VNO)
and Pheromones

Mating behavior
Territorial behavior
Other conspecific behavior


-VNO is located in pit in base of nose
-goes to accessory olfactory bulb
-projects to medial amygdala


Vomeronasal Organ
Secondary Olfactory
System
Sensory neurons synapse
onto an Accessory
Olfactory Bulb
Mouse:
at base of nasal cavity
responds to bodily fluids
introduced into the cavity
(non-volatile)
The Pheromone detector?
MOB detects pheromones
as well
– terminate in microvilli

Mating Behavior

Anecdote about male hamster
Androstenone


Behaviors Mediated by Vomeronasal Organ and Main
Olfactory Epithelium

From Mombaerts

•Aggressive behavior •Discrimination of
•Mating partner preference general odors (instrumental
•Vocalizations conditioning, habituation/
•Endocrine effects (e.g. puberty dishabituation?)
delay, synchronization of estrous)

Human Pheromones?
Anecdotal: man’s whisker growth faster in
the presence of women
Women who live together tend to get their
period during the same time of the month.
Chemicals collected from the armpit and
dabbed under the nose have the same effect
on women
One chemical will shorten the menstrual cycle
by 1.7 days
Another chemical will lengthen the cycle by 1.4
days

MHC

Major Histocompatibility Complex
Identified as a major component in tissue graft
rejection
Also appears to influence our body odor
Mechanism for detecting people with
similar (or different) genotypes?


Human VNO?
Human fetus
have a VNO
but connections appear to
disappear after ~19 weeks
of age
Adult:
usually a depression (or
pit) in nasal cavity
not always there or on
both sides
most human VNO
Receptors are
pseudogenes... Introductory Neurobiology 2012

“When, from a long-distant past nothing remains,
After the people are dead;
after the things are broken and scattered.
Still, alone, more fragile,
but with more vitality,
more insubstantial,
but more persistent, more faithful,
the smell and taste of things remain poised forever,
like ghosts, ready to remind us…

Remembrance of Things Past
––––Marcel Proust

14 Olfaction 2012-1

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