The Olfactory System

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The Olfactory System
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Olfactory System Chemical sensing system with
receptor organs in the nasal passages Receptors
synapse directly into the brain heavy
connections with the limbic system Different
from other sensory systems in many ways
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Olfactory System Peripheral Structure Olfactory
receptors are located on the olfactory (or nasal)
epithelium. The epithelium hangs down from the
roof of the nasal sinus. The epithelium contains
olfactory receptor cells and supporting cells.
BRAIN
Dendrites of olfactory receptor cells extend into
the mucus coating of the epithelium odorant
molecules bind to receptors on the dendrites.
Axons of the olfactory receptor cells enter the
brain and synapse on cells in the olfactory bulb.
SINUS
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Olfactory sensory neurons
There are about 10 million receptors per side in
humans
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Olfactory sensory neurons
No circuitry or synapses in the epithelium
receptors have axons (thin, unmyelinated, slow)
which project directly to the brain. Receptors
die and are replaced about every 60 days.
Stem cell
To olfactory bulb
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Olfactory receptors use a G-protein coupled
transduction mechanism similar to visual receptors
http//users.rcn.com/jkimball.ma.ultranet/BiologyP
ages/O/Olfaction.html
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Olfactory receptors show strong adaptation
Adjust sensitivity
Kinase
Mechanisms 1. Kinase phosphorolation of receptor
protein (desensitization to odorant molecules)
2. Adjustment of channel sensitivity to cAMP (up
or down depending on odorant concentration)
http//users.rcn.com/jkimball.ma.ultranet/BiologyP
ages/O/Olfaction.html
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What exactly do receptors code?

• How odors are encoded by the olfactory receptors
  was a long-standing mystery
• Early olfactory researchers suggested that a
  small number of receptor types could encode a
  large number of natural odors, similar to 3 cones
  coding all perceived colors The Prime Odor
  theory (7 primes was a popular number)
• Difficult to determine what those prime odors
  might be and how they would be combined to give
  the smell of a natural substance

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Richard Axel and Linda Buck used molecular
techniques to determine the number of different
olfactory receptor types. The concept and
strategy
3. LOCALIZE THE EXPRESSED GENES BACK TO THE
OLFACTORY RECEPTOR CELLS
1. SPECIFICITY WOULD BE BASED ON STRUCTURE OF
RECEPTOR-G PROTEIN COMPLEX THEREFORE, IF YOU
DETERMINE THE NUMBER OF DIFFERENT RECEPTOR
STRUCTURES, YOU KNOW THE NUMBER OF DIFFERENT
FUNCTIONAL TYPES, AND THEREFORE THE NUMBER OF
DIFFERENT PRIME ODORS
2. STRUCTURALLY DIFFERENT RECEPTOR PROTEINS
WOULD BE CODED BY DIFFERENT GENES CLONE,
SEQUENCE, CHARACTERIZE GENES EXPRESSED IN THE
OLFACTORY EPITHELIUM, LOOK FOR SYSTEMATIC
VARIATION ON G-PROTEIN TYPES
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• Result There are 1000 different genes in 4
  families each codes 7-transmembrane domain
  G-protein coupled receptor protein that is
  expressed in olfactory receptors in mice
• About 350 of these are functional genes in
  humans the rest are present as pseudogenes
• Each receptor cell in the epithelium expresses
  only one receptor gene
• Therefore, each receptor is best tuned to one
  of 1000 different chemical types
• What these types are is still not clear, nor is
  how the code gets turned into a smell

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The olfactory epithelium is mapped, but not in
a familiar way
The 4 gene families are expressed in different
zones of the epithelium
http//nobelprize.org/medicine/laureates/2004/buck
-slides.pdf
Within a zone, different receptor types appear to
be randomly scattered
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Examples of odorant coding note that relative
levels of activation in the different receptors
might also be important in coding the odor
http//nobelprize.org/medicine/laureates/2004/buck
-slides.pdf
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A combinatorial code means that receptors can
contribute to the perception of very different
smells
http//nobelprize.org/medicine/laureates/2004/buck
-slides.pdf
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Output of the olfactory epithelium goes to the
Olfactory Bulb Olfactory bulb is a three layered
structure. Mitral cells are the principal neurons
of the olfactory bulb.
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Olfactory Bulb Circuitry The glomerulus is the
basic processing component of the olfactory bulb
Olfactory Bulb Circuitry Periglomerular cells in
the glomerulus and granular cells in the deeper
layers mediate local and lateral inhibition
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Cells expressing a single type of receptor are
widely scattered across the olfactory epithelium.
Axons of all these cells converge on a single
place (glomerulus) in the olfactory bulb.
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All the axons terminating in a glomerulus are
from the same type olfactory receptors. Therefore
each glomerulus codes one odorant type.
Axons from each olfactory receptor type terminate
in very few (maybe only 1 or 2) glomeruli at one
point in the olfactory bulb.
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STRUCTURE OF THE OLFACTORY GLOMERULUS
A glomerulus is a self-contained zone of synaptic
interactions. There are about 2000 glomeruli in
the olfactory bulb of each side.
Axons from 25,000 olfactory receptors
10,000,000 RECEPTORS
Periglomerular cells form inhibitory connections
between glomeruli
2,000 GLOMERULI
Dendrites from 25 mitral cells
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SCIENCE VOL 286 22 OCTOBER 1999
Olfactory system codes odors based on chemical
structure of molecules specificity is for a
molecular structural characteristic, not a
particular molecule.
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Dendrodendritic reciprocal synapses form between
PG cells and MT dendritic tufts, and between
granular cells and MT basal dendrites. These both
result in local dendritic inhibition following
excitation of the mitral cells by olfactory nerve
inputs. (NOTE This is in addition to lateral
inhibition of neighboring mitral cells.)
http//flavor.monell.org/7Eloweg/OlfactoryBulb.ht
m
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Lateral inhibition through periglomerular cells
Looking down on glomerular level connections
form /- center surround receptive field
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Oscillations induced through dendrodendritic
connections
Mitral EPSP

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Mitral AP
Odorant present
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Olfactory pathways out of the bulb are all
uncrossed. The piriform cortex is considered the
olfactory sensory cortex.
Numerous connections to limbic system
areas. Connections to cortical areas do not
depend on relay through a thalamic nucleus
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Cortical representation of olfactory information
SCIENCE VOL 294 9 NOVEMBER 2001
Single glomeruli project to multiple locations in
olfactory cortex.
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http//nobelprize.org/medicine/laureates/2004/buck
-slides.pdf
Glomeruli projections overlap in olfactory
cortex, and individual cortical neurons receive
input from multiple glomeruli (and hence receive
input from multiple odorants).
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QUESTION Why remix inputs after you have gone
through all the trouble of separating them out so
effectively?
ANSWER Olfaction may be based on pattern
detection Cortical neurons are concerned with
specific combinations of inputs, with each
combination corresponding to a percept.
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The Vomeronasal System A second olfactory system
is present in most vertebrates. It is separate
from the main olfactory system anatomically and
functionally.
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The vomeronasal organ is separate from the main
olfactory epithelium in the nasal cavity
http//bioweb.usc.edu/courses/2002-fall/documents/
neur524-olfactory_transduction.pdf
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Vomeronasal receptors are different from main
olfactory receptors
About 100 different receptor types in two gene
families these families are different from the
four in which main olfactory receptors are coded
Vomeronasal receptors use a different signal
transduction pathway than main olfactory receptors
http//bioweb.usc.edu/courses/2002-fall/documents/
neur524-olfactory_transduction.pdf
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The vomeronasal system is specialized for
detecting high molecular weight, relatively
nonvolatile chemicals. Its presence is often
accompanied by morphological or behavioral
specializations for moving such odorants to the
vomeronasal epithelium.
STEREOTYPED BEHAVIORS TONGUE FLICKING IN SNAKES
FLEHMEN RESPONSE IN HORSES
VASCULAR PUMPS
LOCATION NEAR NARES, OR OPENING INTO MOUTH CAVITY
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The vomeronasal receptors project to a separate
accessory olfactory bulb via a separate
accessory olfactory nerve
Organization of the AOB is similar to that of the
MOB. Outputs are different the AOB output target
only subcortical limbic areas that connect in
turn to the hypothalamus
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PHEROMONES PREY ODORS
GENERAL ODORS
Vomeronasal Organ
Main Olfactory Organ
Accessory Olfactory Bulb
Main Olfactory Bulb
Olfactory Cortex
Medial, BNST
Cortical
Septal nuclei
Amygdala
Olfactory tubercle
Entorhinal Cortex
Hypothalamus
Hippocampus
PARALLEL OLFACTORY PATHWAYS
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• The vomeronasal system is specialized for
  detecting and processing biologically important
  odors, especially chemical communication signals
  (pheromones)
• Chemical communication is a preeminent social
  communication channel in most mammals
• Courtship, sexual behavior, aggression, maternal
  behavior, kin recognition, pair bonding,
  territoriality, fear and predator avoidance all
  involve chemical signaling and are controlled by
  the reception of chemical signals in most mammals
• Lesions of the vomeronasal system at various
  levels interfere with normal social behavior
  mediated by pheromonal communication

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Vomeronasal and Main Olfactory System May Both
Participate in Chemical Signaling Depending on
Experience
In virgin male rodents, lesioning VNO blocks sex
with a female lesioning OE has no effect
X
X
NO COPULATION WITH A FEMALE
NORMAL COPULATION WITH A FEMALE
In male rodents with 1 previous sexual
experience, lesioning VNO or OE alone has no
effect both must be lesioned to block copulation
X
X
X
X
NO COPULATION WITH A FEMALE
NORMAL COPULATION WITH A FEMALE
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Is Chemical Communication Important in Humans?

• Do we have a vomeronasal organ? Probably not (nor
  do Old World primates generally) but does that
  mean anything?
• What can we recognize by odor alone? The
  t-shirt experiments
• Can odors affect reproductive function? The
  menstrual synchrony experiments
• If human pheromones were controlling our
  behavior, would we even know it? Look where
  accessory olfactory information is sent in the
  brain its all subcortical