A SEMINAR ON

OLFACTION

• Dr.Divyesh L. Prajapati
• First Year P.G. Student
• Department of Physiology
 0utlines
• Introduction
• Site of olfaction
• Olfactory pathways
-- Olfactory nerves
-- Olfactory bulb
-- Olfactory tracts
-- Olfactory cortex
• Physiology of olfaction
-- Odoriferous stimuli
-- Olfactory receptors and transduction
of olfactory information
-- proccessing of olfactory sensation in
olfactory bulb
-- Transmission of information to
olfactory cortex and neocortex
• Factors affecting olfaction
• Abnormalities of olfaction
• Etiologies of Olfactory
Dysfunction
• Olfactory measurement
 Comparision of General and
Special Senses
General Senses Special Senses
• Include somatic • Include smell, taste,
sensations (tactile, vision, hearing and
thermal, pain, and equilibrium
proprioceptive) and • Concentrated in
visceral sensations. specific locations in
• Scattered throughout the head.
the body.
• Anatomically distinct
structures.
• Simple structures. • Complex neural
pathway.
 Introduction
• Olfaction :
-means sense of smell.

• Macrosmatic :
- well developed in animal like dog and
rabbit

- give warning of the environmental changes.

• Microsmatic :
- comparatively less developed in
humans, apes and monkeys(primates).

-Important for pleasure and for enjoying

the taste of food.
 Site of olfaction
• Olfactory mucosa of nose in humans.
• Vomeronasal organ in reptiles and certain
animals.
• In both these structures, the free nerve
endings of the olfactory nerves having
specialized receptors is present which
detects olfactory stimuli.
 Olfactory Membrane
Location :
-the superior part of
each nostril.

-a surface area of
about 2.4 square
centimetres in each
nostril.
Histology of olfactory membrane

-consists of three types of cells.

1. olfactory cells
2. supporting cells or sustentacular
cells
3. basal cells
Olfactory membrane
 Olfactory cells
• The receptor cells for the smell sensation.

• actually bipolar nerve cells.

• about 100 million of these cells in the

olfactory epithelium lies in between the
supporting cells.
• The dendrites of the olfactory cell

knob

4 to 25 olfactory hairs (olfactory cilia)

mucus that coats the inner surface of nasal cavity

and form a dense mat.
• It is these cilia that react to odours in the
air and stimulate the olfactory cells.

• Their axons are fine unmyelinated fibres.

• Bundles of these fibres become

ensheathed as a group by Schwann cells,
forming the olfactory nerve.
• Characteristic features of olfactory
cells:
1. only sensory neurons whose cell bodies
are closest to external environment.

2. short life span of about 60 days and

replacement by proliferation of basal cells
Supporting / Sustentaculer cells
• Collumnar in shape.
• Microvilli extend from the surface of these
cells into the mucus layer.
• Functions
1.deactivate odorants
2.protecte the epithelium from foreign
agents
3.do not generate action potentials
 4.do not seem to contribute transduction
process
5.Secrete mucus.
• Bowman’s glands:
-Located just under the basement
membrane
-Also secrete mucus
 Basal cells
• Progenitor cells from which the other cell
types differentiate to replace the olfactory
receptors
• “Stem cell”
• Continuous replacement of receptor cells
by mitosis of basal cells.
• BMP ( bone morphogenic protein ) has
role in these process.
 Distinguishing features of
olfactory mucosa from
respiratory mucosa
• Presence of receptor cells.
• Presence of bowman’s glands.
• Presence of a distinctive yellow brown
pigments.
• Absence of rhythmic ciliary beating
Respiratory and olfactory mucosa
 Nerve supply of olfactory
mucosa
• Special sensory nerves :

- Olfactory nerve ( 1st cranial nerve )

- mediates odour sensation &
responsible for determining flavours
• General sensory nerves :
- Trigeminal nerve ( 5th cranial nerve )
e.g.. Vapors of ammonia
 Vomeronasal organ
• Not well developed in humans but
developed in nose of some animals like
rodents.
• Pouch like structure found along the nasal
septum.
• Receptors present here
- concerned with perception of odour that
comes from pheromones and foodstuffs
and thus related to sex and eating behavior of the
animal.
Vomeronasal organ

Accessory olfactory bulb

Amygdala and Hypothalamus.

 Pheromones
• Hormone like substances
• Emit specific odour
• Produce hormonal,behavioral or other
physiological changes in another animal of
same species.
• Secreted during mating season only.
• The smell of it often is the cause of sex,
which an animal follows to find out its
matting partner which may be waiting at
distance
• Assumed that pheromones also present in
human being and concerned with smell
and sexual function.
• Human pheromone refined from urine,
axilary secretion, vaginal secretion
 Olfactory pathways
• Consists of
1. Olfactory nerves
2. Olfactory bulb
3. Olfactory tract
4. Olfactory cortex
 1.Olfactory nerves
• 1st cranial nerves
• Consists of the axons of the bipolar
olfactory neurons.
• Pierce the cibriform plate on either side to
reach olfactory bulb.
 2.Olfactory bulb
• Oval flattened strip of grey matter
• On cribiform plate
• Point to point representation of olfactory
mucosa
Upper part of mucosa -- anterior part
Lower part of mucosa – posterior part
• Three types of cells
1. Mitral cells
2. Tufted cells
3. interneurons
- Granule cells
- periglomeruler cells
 Mitral cells
And Tufted cells
• Dendrites of these cells form synapses
with the axon terminals of olfactory
neurons ---globular masses called
olfactory glomeruli
• About 1000 axons of olfactory neurons
synapse on the dendrites of a single mitral
cell.
• Axons of these cells leave the olfactory
bulb and run in the olfactory tract.
 Granule cells and periglomeruler
cells
• Inhibitory neurons.
• They form dendro-dendritic reciprocal
synapses with the dendrites of the mitral
cells.
• periglomeruler cells also participate in the
formation of olfactory glomeruli
Basic neural circuit in olfactory bulb
 3.Olfactory tract
• Olfactory sulcus on the orbital surface of the
frontal lobe.
• proceeds backwards from each olfactory bulb to
the region of anterior perforated substance on
the base of brain
• It divides into lateral,intermediate and medial
olfactory striae

Olfactory trigone
– a flattened part of the olfactory tract near the
anterior perforated substance before it divides
into the striae
Olfactory tract
Anterior olfactory nucleus
• Scattered neurons within olfactory tract
• These neurons receive synaptic
connections from neurons of olfactory bulb
• Send axons through the anterior
commissure to excite inhibitory neurons on
the contralateral olfactory bulb
Olfactory stria
• Three stria are derived from each olfactory
tract
• Lateral olfactory stria :
- axons of these stria synapse in the
primary olfactory receiving area which
includes the pre-piriform cortex and in
many animals the piriform lobe
• Medial olfactory stria:
- projections to the amygdaloid nucleus as
well as to part of the cortex of the basal
forbrain
• Intermediate olfactory striae:
- terminates in the olfactory tubercle,an
area of the cortex rostral to the anterior
perforated substance
 4.Olfactory cortex
• Anterior olfactory nucleus
• Prepiriform cortex
• Olfactory tubercle
• Amygdala

• These all are parts of limbic system.

 Physiology of olfaction
• Odoriferous stimuli
• Olfactory receptors and transduction in the
olfactory receptor neurons
• Processing of olfactory sensation in
olfactory bulb
• Transmission of odorant information to the
olfactory cortex and neocortex
• Role of different regions of olfactory cortex
and neocortex
 Odoriferous stimuli
• Odorants enter the nasal cavity while
breathing.
• During quite breathing,air passes through
lower parts of nasal cavity,but through
eddy currents,some air does reach the
olfactory epithelium.
• Sniiffing
-act of deep breathing which occurs
when new odour is encountered
-Semi-reflex response
• Odorant molecule : to be effective,
1.volatile – as olfactory receptors respond
to chemicals transported by air into nose

2.water soluble -- to penetrate the watery

mucuos layer to reach olfactory receptors
3.lipid soluble – to penetrate the cell
membrane of olfactory receptor cells to
stimulate those cells.
Types of odorant stimuli

• Over 50 primary smell sensation in

contrast to three primary sensation for
colour and four primary sensation for taste
• Humans are able to percieve more than
10000 differant odours.
• Common odours
1.aromatic – camphor,cloves and lavender
2.frangant – perfumes and flowers
3.etheral -- ether and chloroform
4.garlic -- garlic,onion and sulpher compounds
5.burning – tobacco,feather,and meat
6.nauseating – excreta,decomposed meat and
vegetables
7.goat – sweat,ripe cheese
8.repulsive – bed bug
9.musky -- musk
 Olfactory receptors
• Cilia of olfactory neurons are specialised
for smell detection

• they have specific receptors for odorants

as well as the transduction machinery to
amplify sensory signals and generate
action potentials in the neuron’s axon.
• Important features:
1. Olfactory receptors belongs to a large
superfamily of structurally related proteins
that trasduce signals by interaction with G
protein
2. permits discrimination of large variety of
odorants.
3. a large multigene family appears to code
for as many as 1000 types of odorant
receptors
 Steps in transduction in the
olfactory receptor neurons
• Binding of odorant molecule to receptors

• Activation of receptor

• Depolarization receptor potential

• Action potentials
1) Binding of odorant molecule to
receptors
• Odorant molecules entering the nasal
cavity dissolved in the mucous layer
covering the olfactory mucosa which
contains odorant binding proteins (OBP).
• odorant binding proteins (OBP)
concentrate and transfer the odorant
molecules to the receptor present on the
cilia of olfactory neurons
2) Activation of receptors
• The interaction between odorant with its
receptor causes interaction between the
receptor and a heterotrimetric G-protein
• Induce release of the G-protein GTP
coupled alpha subunit
• Stimulates adenyl cyclase to produce
cAMP
3) Depolarization receptor potential
• The increased intracellular cAMP opens
cyclic nucleotide gated (CNG) cation
channels, leading to cation influx and a
change in membrane potential in the
cilium membrane,i.e.produces a
depolarizing receptor potential
4) Action potentials
• The receptor potential depolarizes the
initial segment of the axon to threshold
leading to generation of action potentials
in the sensory axons and the transmission
of signal to olfactory bulb.
signal transduction in olfactory receptor neuron
 Processing of olfactory
sensation in olfactory bulb
• Odorant information is encoded spatially in
olfactory bulb.
• There is lateral inhibition mediated by
periglomerular and granule cells in
olfactory glomeruli.
• The multiple inputs to olfactory bulb from
olfactory area of cortex as well as the
basal portion of forebrain and midbrain is
another source of signal refinement.
 Transmission of odorant
information to the olfactory
cortex and neocortex
• Olfactory bulb

• Olfactory cortex

• Frontal cortex directly and Orbitocortex via

thalamus
• Olfactory pathway is the only sensory
system that does not have an obligatory
synaptic relay in the thalamus.
• This reflects the phylogenetic
primitiveness of the olfactory system.
• However, olfactory information may reach
the medio-dorsal nucleus of the thalamus
and then to the prefrontal and orbitofrontal
cortex
Role of different regions of cerebral cortex
• Piriform cortex
– activated by sniffing
• Amygdala and Hypothalamus
-- emotional and motivational response
--In animals, effects of pheromones are
thought to be mediated by signals from the
main and accessory olfactory bulbs to
amygdala and hypothalamus
• Entorhinal cortex
-- olfactory memories
• Neocortex (frontal and orbitofrontal cortex)
-- conscious discrimination of odors
 Factors affecting olfactory
function
• 1) Threshold of olfactory receptor
• 2) intensity/concentration of the odour
• 3) Structural configuration of odorant
• 4) Adaptation
1) Threshold of olfactory receptors
--varies from substance to substance
--Threshold concentration of some
substances
Substance mg/L of Air
Ethyl ether 5.83
Chloroform 3.30
Pyridine 0.03
Oil of peppermint 0.02
lodoform 0.02
Butyric acid 0.009
Propyl mercaptan 0.006
Artificial musk 0.00004
Methyl mercaptan 0.0000004
2) intensity/concentration of the odour
-- the concentration of an odoriferous
substance must be changed by 30%
before a differance can be detected.
-- high water and lipid solubility are
characteristic of substances with strong
odour.
3) Structural configuration of odorant

--small and contain 3-20 carbon atoms

--molecules with the same number of
carbon atoms but different structural
configuration have differant odours
4)Adaptation
-- Adapts very rapidly with continued
exposure to an odour.
-- Mechanisms:
1. inactivation or desensitization of the
receptor due to phosphorylation of the
receptor by a protein kinase following an
odorant receptor with its ligand
2.adjustment in the sensitivity of cyclic
nucleotide-gated ion channels
-- It is mediated by Ca2+ acting via
calmodulin on cyclic nucleotide-gated
(CNG) ion channels.
--When CNG A4 is knocked out,
adaptation is slowed.
 Abnormality of olfaction
• Anosmia : inability to detect qualitative
olfactory sensations (i.e., absence of smell
function)
• Partial anosmia : ability to perceive some,
but not all, odorants
• Hyposmia or microsmia : decreased
sensitivity to odorants
• Hyperosmia : abnormally acute smell
function
• Dysosmia : Distorted detection of smell of
smell.
- Cacosmia - Inappropriate detection of a
normal smell as foul or unpleasant
- Parosmia - Perversion of sense of smell
- Heterosmia - Inability to distinguish
between certain odors
 - Agnosia - Inability to classify or contrast
odors,although able to detect odors
• Phantosmia : dysosmic sensation
perceived in the absence of an odor
stimulus (known as olfactory hallucination)
Three mechanism of olfactory abnormality
1) conductive or transport impairments :
--obstruction of nasal passages
(e.g. chronic nasal inflamation,polyps,
atrophic rhinitis)
2) sensorineural impairments : damage to
neuroepithelium
(e.g. viral infection, airborne
toxins,kallaman syndrome etc.)
3) central olfactory neural impairment :
-- central nervous system damage (e.g.
tumors, masses impacting on olfactory
tract, neurodegenerative disorders)
 Etiologies of Olfactory
Dysfunction
• Post-URI
• Port traumatic olfactory loss
• Nasal & sinus disease
• Aging
• Congenital
• Neoplasm
• Epilepsy , HIV
• Surgery
• Medication
• Psychiatric disorder
• Toxic exposure
• Endocrine disorder
• Nutitional & metaboloic disorder
1)Post-Upper Respiratory Tract Infection
• most frequent cause of smell loss in the
adult
• Viruses cause edema and hyperemia of
nasal membranes, necrosis of cilia, and
cellular destruction
• Biopsy studies of olfactory epithelia greatly
reduced numbers of olfactory receptors
• replacement of sensory epithelium with
respiratory epithelium
2) Post-traumatic Olfactory Loss
• may be caused by several mechanisms
– Sinonasal tract alteration
– shearing injury of olfactory nerve
filament,
– brain contusion and
– hemorrhage within the olfactory-related
brain regions
3) Nasal and sinus disease
• Inflammation, Polyps, Secondary edema
from ostiomeatal complex pathology
• Obstruction of nasal vault or area through
which airflows get to the olfactory cleft
• Chronic inflammation may be toxic to
olfactory neurons
4) Congenital
• Begin at 8 yrs
• Most other chemosensory function intact
• Specific anosmia
(musk,trimethylamine,hydrogen cyanide)
• Familial anosmia associate premature
baldness,vascular headache
5) Toxic exposure
• The majority of agents related to olfactory
loss are either gases or aerosal eg.
Cigarette smoke , Acetone, cadmium,
chalk, lead, nickle, nitrous gas
• Concentration and length of time exposure
• Olfactory loss reversible or permanent
6) Aging
• Ofactory identification ability drop in 6th &
7th decade
• Olfactory threshold increase with age (less
dramatic in woman than men)
• Dementia-related disease
- Alzheimer’s disease
- Parkinson’s disease
• Damage to olfactory bulb or central
olfactory cortex
• Loss of olfactory detection & recognition
ability
• Alzheimer : neurofibrillary tangle &
neuritic plaque in central olfactory pathway
• Decrease olfactory ability early symptoms
of Alzheimer
• Parkinson : neuronal loss in olfactory bulb
& tract
7) HIV
• Decreased olfactory ability
• Do not correlate with measures of health
like CD4, body weight, management or
diet
8) Epilepsy
• Olfactory auras
• Often last only 2-3 minutes, unpleasant
odor
9) Medication
• Olfactory ability return after discontinue
medication
• Sometimes permanent loss
• Antithyroid drugs:propylthiouracil ,
methimazole
• Antimicrobial drugs:macrolide,
tetracycline,amphotericine B
• Antirheumatoid drugs:colchicine,gold
10) Neoplasm
• Intranasal : Blocking the airflow to the
olfactory cleft
- Inverted papilloma,adenomas,SCCA
• Intracranial : local destruction to olfactory
apparatus
- Menigioma,pituitary tumor, glioma,
frontal lobe tumors ,paraoptic chiasma
tumor
- 25 % temporal lobe tumor cause
olfactory disturbance (hallucination of a
bad smell.)
11) Surgery
• Rhinoplasty
• Sinus and nasal surgery
--advance endoscopic surgery have more
accurate and less olfactory damage
• Cranial and skull base surgery
- frontal or temporal lobe resection
- total or permanent loss of ability
12)Endocrine
• Addison’s disease
• Cushing ‘s syndrome
• Diabetes meliitus
• Hypergonadotropic hypogonadism
• Hypothyroidism
• Panhypopituitarism
• Pregnancy ,menses
13) Nutitional and metabolic
• Chronic alcoholism
• CRF
• Liver cirrhosis
• Trace deficiency : Zinc, copper
• Vitamin deficiency : Vitamin A, B6, B12
 Olfactory measurement
• Olfactory threshold tests :
-detection threshold, recognition threshold
1.PEA tests (University of Pennsylvania) :
phenyl ethyl alcohol
2.CCCRC olfactory test (University of
Connecticut) : butanol
• Olfactory identification test
1.UPSIT (University of Pennsylvania Smell
Identification Test)
• UPSIT (University of Pennsylvania Smell
Identification Test) :
• Dr. Richard Doty
• 10 microencapsulated odors in a“scratch-
and sniff” format
• four response alternatives accompanying
each odor
• normosmia,mild microsmia, moderate
microsmia,severe microsmia, anosmia and
probable malingering
 Electrophysiologic test
• OERPs : odor event-related potential
• EOG : electroolfactogram
• Brain-evoked potential
• BEAM ( The brain electrical activity
monitoring)
• Referances :
• Textbook of Physiology—by Guyton and
Hall
• Textbook of Physiology—by Ganong
• Internet
Thank You