ns_olfaction ppt.ppt
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The Olfactory System
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Olfactory System
Chemical sensing systemwith receptor organs in the
nasal passages
Receptors synapsedirectly into the brain;
heavy connections with
the limbic system
Different from othersensory systems in many
ways
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Olfactory System: Peripheral
StructureOlfactory receptors are located on the
olfactory (or nasal) epithelium. The
epithelium hangs down from the roof ofthe nasal sinus. The epithelium
contains olfactory receptor cells and
supporting cells.
Dendrites of olfactory receptor
cells extend into the mucus
coating of the epithelium;
odorant molecules bind toreceptors on the dendrites.
Axons of the olfactory
receptor cells enter the brain
and synapse on cells in the
olfactory bulb.
BRAIN
SINUS
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Olfactory
sensory
neurons
There areabout 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 arereplaced about
every 60 days.
Stem cell
To olfactory bulb
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http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/O/Olfaction.html
Olfactory receptors use a G-protein coupled
transduction mechanism similar to visual receptors
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http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/O/Olfaction.html
Kinase
Olfactory receptors show strong adaptation
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)
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What exactly do receptors code?
How odors are encoded by the olfactory receptors was along-standing mystery
Early olfactory researchers suggested that a small number
of receptor types could encode a large number of naturalodors, similar to 3 cones coding all perceived colors: ThePrime Odor theory (7 primes was a popular number)
Difficult to determine what those prime odors might beand how they would be combined to give the smell of anatural 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:
1. SPECIFICITY WOULD BE
BASED ON STRUCTURE OF
RECEPTOR-G PROTEIN
COMPLEX; THEREFORE, IF YOUDETERMINE 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
3. LOCALIZE THE
EXPRESSED
GENES BACK TO
THE OLFACTORY
RECEPTOR
CELLS
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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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http://nobelprize.org/medicine/laureates/2004/buck-slides.pdf
The olfactory
epithelium is
mapped, but not in
a familiar way
The 4 gene families are
expressed in different zones of
the epithelium
Within a zone, different
receptor types appear to
be randomly scattered
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http://nobelprize.org/medicine/laureates/2004/buck-slides.pdf
Examples of odorant coding; note that relative levels of
activation in the different receptors might also be
important in coding the odor
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http://nobelprize.org/medicine/laureates/2004/buck-slides.pdf
A combinatorial code
means that receptors
can contribute to theperception of very
different smells
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Output of the olfactory epithelium goes to the
Olfactory Bulb: Olfactory bulb is a three layeredstructure. Mitral cells are the principal neurons of the
olfactory bulb.
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Olfactory Bulb Circuitry:
The glomerulus is thebasic processing
component of the
olfactory bulb
Olfactory Bulb Circuitry:
Periglomerular cells in the
glomerulus and granularcells in the deeper layers
mediate local and lateral
inhibition
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Cells expressing
a single type of
receptor are
widely scatteredacross 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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Axons from 25,000 olfactory receptors
STRUCTURE OF THE OLFACTORY GLOMERULUS
Dendrites from 25 mitral cells
Periglomerular cells form
inhibitory connections between
glomeruli
A glomerulus is a self-
contained zone of synapticinteractions.
There are about 2000
glomeruli in the olfactory
bulb of each side.
10,000,000
RECEPTORS
2,000
GLOMERULI
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Olfactory system codes odors based on chemical structure of molecules;
specificity is for a molecular structural characteristic, not a particular molecule.
SCIENCE VOL 286 22 OCTOBER 1999
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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.htm
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Lateral inhibition through periglomerular cells:
+ ---
-
Looking down on glomerular level;connections form +/- center surround
receptive field
+
_
Oscillations induced through dendrodendritic connections:
Mitral EPSP
Mitral AP
Odorant present
Olfactory pathways out of the bulb are all
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Numerous connections to limbicsystem areas.
Connections to cortical areas do
not depend on relay through a
thalamic nucleus
Olfactory pathways out of the bulb are all
uncrossed.
The piriform cortex is considered the
olfactory sensory cortex.
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SCIENCE VOL 294 9 NOVEMBER 2001
Single glomeruli project to multiple locations in olfactory cortex.
Cortical
representation
of olfactoryinformation
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Glomeruli projections overlap in olfactory cortex, and
individual cortical neurons receive input from multiple
glomeruli (and hence receive input from multiple odorants).
http://nobelprize.org/medicine/laureates/2004/buck-slides.pdf
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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 use a
different signal
transduction pathway
than 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 are different from 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 oftenaccompanied by morphological or behavioral
specializations for moving such odorants to
the vomeronasal epithelium.
LOCATION NEAR
NARES, OR
OPENING INTO
MOUTH CAVITY
VASCULAR
PUMPS
STEREOTYPED
BEHAVIORS: TONGUE
FLICKING IN SNAKES
FLEHMEN RESPONSE
IN HORSES
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The vomeronasal receptors project to a
separate accessory olfactory bulb via aseparate accessory olfactory nerve
Organization of the AOB is similarto 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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Accessory Olfactory
Bulb
Main Olfactory
Bulb
Vomeronasal Organ Main Olfactory Organ
Septalnuclei
Amygdala Olfactorytubercle
Olfactory
Cortex
PHEROMONES
PREY ODORSGENERAL ODORS
EntorhinalCortex
Hippocampus
PARALLEL OLFACTORY PATHWAYS
Medial,
BNSTCortical
Hypothalamus
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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, maternalbehavior, 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
XX
X
NO COPULATION WITH A FEMALE
NO COPULATION WITH A FEMALE
NORMAL COPULATION WITH A FEMALE
NORMAL COPULATION WITH A FEMALE
XX
In male rodents with 1
previous sexualexperience, lesioning
VNO or OE alone has
no effect; both must
be lesioned to block
copulation
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Is Chemical Communication Important in Humans?
Do we have a vomeronasal organ? Probably not (nor doOld World primates generally)but does that meananything?
What can we recognize by odor alone? The t-shirtexperiments
Can odors affect reproductive function? The menstrualsynchrony experiments
If human pheromones were controlling our behavior,would we even know it? Look where accessory olfactoryinformation is sent in the brainits all subcortical