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Domina Petric, MD
 Olfaction begins with airborne molecules interacting
with receptors.
 Receptors are located in olfactory epithelium: dorsal
and medial aspect of nasal passage.
 Receptor cells grow axons that pass through the
perforations of the ethmoid bone: the cribriform
plate.
 Axons enter into the olfactory bulb and synapse with
neurons in the olfactory bulb.
Olfactory pathway
 Axons that grow from receptor cells are first cranial
nerve and olfactory bulb is actually part of the
brain.
 Olfactory bulb extends into the lateral olfactory
tract: it is an extension of the brain.
 Lateral olfactory tract is made of MITRAL cells.
 The mitral cells are the principal projection cells
that connect the olfactory bulb to the rest of the
brain.
Olfactory pathway
Olfactory
receptors
Primary axons are
first cranial nerve.
Olfactory
bulb
Axons of
the mitral
cells make
lateral
olfactory
tract.
Targets of the
olfactory
bulb (the
olfactory
cortex):
A) Pyriform
cortex
B) Olfactory
tubercle
C) Amygdala
D) Entorhinal
cortex
Pyriform cortex and entorhinal cortex
are cortex structures
(laminar cell organisation).
Entorhinal cortex is associated
with hippocampal formation.
Olfactory tubercle and amygdala
are corticoid structures.
Structures of olfactory cortex, both cortical and
corticoid structures are interconnected with
each other and connected with other structures
like thalamus, hypothalamus and
orbitofrontal cortex.
In the orbitofrontal cortex all the informations
from chemosensory systems (oflaction, gustation,
trigeminal chemoreception) is combined with
somatic sensation and visual sensation.
In this part of the brain the concept of flavour is
represented and sense of rewarding value of food.
Orbitofrontal cortex
http://serendip.brynmawr.edu
AnatomyOlfactory
tubercle
Olfactory
bulb
Lateral
olfactory
tract
Pyriform
cortex
Amygdala
There is no obligatory thalamic relay
between the olfactory bulb and olfactory
cortex.
There is no known map of the sensory
environment.
Olfaction
 Spindle shaped cells are mature olfactory receptor
neurons: function of sensory transduction.
 Among basal cell population is a set of neural stem
cells.
 Glandular cells produce thick mucus that covers the
upper part of the olfactory epithelium.
 Odorants pass the mucus and interact with olfactory
cilia: olfactory receptor proteins within the cilia
interact with odorant molecules.
Sensory transduction in the
olfactory epithelium
 The odorant receptor molecule is a G-protein coupled
receptor: interacts with odorant molecule.
 When odorant molecule binds on the receptor, G-olf
protein activates.
 Next target is adenyl cyclase III: activation causes a
production of cAMP.
 High levels of cAMP gate the opening of the cation
selective channel (for sodium and calcium ions).
 Sodium and calcium ions enter the cytoplasm of receptor
neuron cilium: DEPOLARISATION.
Sensory transduction
 High levels of calcium ions in the cytoplasm cause
interaction of calcium ions with CALMODULIN:
that causes gating of chloride channel.
 Opening of the chloride channel causes the eflux of
chloride ions outside the receptor neuron cell.
 This amplifies the depolarisation.
 Interaction of calcium ions with calmodulin has also
impact on cAMP gated cation channel (for sodium
and calcium ions).
Sensory transduction
 The interaction of calcium and calmodulin can
reduce the sensitivity of cation channels to the
binding of cAMP.
 This reduces the influx of sodium and calcium and
reduces the depolarisation causing the OLFACTORY
ADAPTATION.
 There is one more mechanism of adaptation:
sodium/calcium exchanger (sodium ions influx the
cell and calcium ions eflux out of the cell).
Sensory transduction
As calcium efluxes the cell, there is less
interaction of calcium with calmodulin.
This is also a mechanism of olfactory
adaptation to the persistent present of the
same odorant.
Sensory transduction
 Quality of the odorant can be sometimes modulated
by the concentration of the odorant.
 Low concentrations of the odorant INDOLE smell
like flowers, but high concentrations of INDOLE
smell putrid.
 Most odorants are complex molecules.
 Odorant can smell differently regarding the different
molecule rotation (right or left rotation).
Combinatorial olfactory code
Same odorant molecule can
interact with more than one
receptor depending upon the
geometrical configuration of
odorant molecule.
Combinatorial olfactory code
 Mitral cell recieves the synaptic input from an
afferent axon in the structure called GLOMERULUS.
 Periglomerulus neuron is a small interneuron.
 Granule cell is also a small interneuron.
 Interneurons mediate inhibitory interactions within
and among glomeruli.
 Tufted cell contributes postsynaptic targets for the
afferent input that is arriving in the olfactory bulb.
Glomerulus
 Glomeruli are the first site of synaptic connection
between the olfactory epithelium and the brain.
 Each glomerulus recieves input from about 25 000
olfactory receptor neurons.
 All of these 25 000 olfactory receptor neurons express a
receptor that will interact with the same set of odorants.
 All of the olfactory receptor neurons that express the
same olfactory receptor, grow their axons and converge
onto two bilaterally symmetrical glomeruli in the two
olfactory bulbs.
Glomerulus
 Pyriform cortex sends inputs to medial dorsal
thalamic nucleus.
 Both pyriform cortex and medial dorsal thalamic
nucleus are connected to the orbitofrontal cortex.
 Entorhinal cortex is associated with hippocampal
formation: declarative memory.
 The olfactory signals can be important triggers
for the recall of memory.
Olfactory cortex
Olfactory cortex sends inputs to
the hypothalamus.
In the hypothalamus odorants can
engage our visceral motor systems.
Olfactory cortex
Pheromones are detected with special part
of the olfactory epithelium and posterior
part of the olfactory bulb: effect on
motivated behavior in many mammals.
How does this work in humans?
Pheromones
Olfactory function declines with age.
Olfactory receptor neurons can regenerate after,
for example, head trauma.
Stem cells provide this ability.
Functional recovery is never 100%.
https://www.coursera.org/learn/medical-
neuroscience/lecture: Leonard E. White, PhD,
Duke University
http://serendip.brynmawr.edu
Literature

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Olfaction

  • 2.  Olfaction begins with airborne molecules interacting with receptors.  Receptors are located in olfactory epithelium: dorsal and medial aspect of nasal passage.  Receptor cells grow axons that pass through the perforations of the ethmoid bone: the cribriform plate.  Axons enter into the olfactory bulb and synapse with neurons in the olfactory bulb. Olfactory pathway
  • 3.  Axons that grow from receptor cells are first cranial nerve and olfactory bulb is actually part of the brain.  Olfactory bulb extends into the lateral olfactory tract: it is an extension of the brain.  Lateral olfactory tract is made of MITRAL cells.  The mitral cells are the principal projection cells that connect the olfactory bulb to the rest of the brain. Olfactory pathway
  • 4. Olfactory receptors Primary axons are first cranial nerve. Olfactory bulb Axons of the mitral cells make lateral olfactory tract. Targets of the olfactory bulb (the olfactory cortex): A) Pyriform cortex B) Olfactory tubercle C) Amygdala D) Entorhinal cortex Pyriform cortex and entorhinal cortex are cortex structures (laminar cell organisation). Entorhinal cortex is associated with hippocampal formation. Olfactory tubercle and amygdala are corticoid structures. Structures of olfactory cortex, both cortical and corticoid structures are interconnected with each other and connected with other structures like thalamus, hypothalamus and orbitofrontal cortex.
  • 5. In the orbitofrontal cortex all the informations from chemosensory systems (oflaction, gustation, trigeminal chemoreception) is combined with somatic sensation and visual sensation. In this part of the brain the concept of flavour is represented and sense of rewarding value of food. Orbitofrontal cortex
  • 7. There is no obligatory thalamic relay between the olfactory bulb and olfactory cortex. There is no known map of the sensory environment. Olfaction
  • 8.  Spindle shaped cells are mature olfactory receptor neurons: function of sensory transduction.  Among basal cell population is a set of neural stem cells.  Glandular cells produce thick mucus that covers the upper part of the olfactory epithelium.  Odorants pass the mucus and interact with olfactory cilia: olfactory receptor proteins within the cilia interact with odorant molecules. Sensory transduction in the olfactory epithelium
  • 9.  The odorant receptor molecule is a G-protein coupled receptor: interacts with odorant molecule.  When odorant molecule binds on the receptor, G-olf protein activates.  Next target is adenyl cyclase III: activation causes a production of cAMP.  High levels of cAMP gate the opening of the cation selective channel (for sodium and calcium ions).  Sodium and calcium ions enter the cytoplasm of receptor neuron cilium: DEPOLARISATION. Sensory transduction
  • 10.  High levels of calcium ions in the cytoplasm cause interaction of calcium ions with CALMODULIN: that causes gating of chloride channel.  Opening of the chloride channel causes the eflux of chloride ions outside the receptor neuron cell.  This amplifies the depolarisation.  Interaction of calcium ions with calmodulin has also impact on cAMP gated cation channel (for sodium and calcium ions). Sensory transduction
  • 11.  The interaction of calcium and calmodulin can reduce the sensitivity of cation channels to the binding of cAMP.  This reduces the influx of sodium and calcium and reduces the depolarisation causing the OLFACTORY ADAPTATION.  There is one more mechanism of adaptation: sodium/calcium exchanger (sodium ions influx the cell and calcium ions eflux out of the cell). Sensory transduction
  • 12. As calcium efluxes the cell, there is less interaction of calcium with calmodulin. This is also a mechanism of olfactory adaptation to the persistent present of the same odorant. Sensory transduction
  • 13.  Quality of the odorant can be sometimes modulated by the concentration of the odorant.  Low concentrations of the odorant INDOLE smell like flowers, but high concentrations of INDOLE smell putrid.  Most odorants are complex molecules.  Odorant can smell differently regarding the different molecule rotation (right or left rotation). Combinatorial olfactory code
  • 14. Same odorant molecule can interact with more than one receptor depending upon the geometrical configuration of odorant molecule. Combinatorial olfactory code
  • 15.  Mitral cell recieves the synaptic input from an afferent axon in the structure called GLOMERULUS.  Periglomerulus neuron is a small interneuron.  Granule cell is also a small interneuron.  Interneurons mediate inhibitory interactions within and among glomeruli.  Tufted cell contributes postsynaptic targets for the afferent input that is arriving in the olfactory bulb. Glomerulus
  • 16.  Glomeruli are the first site of synaptic connection between the olfactory epithelium and the brain.  Each glomerulus recieves input from about 25 000 olfactory receptor neurons.  All of these 25 000 olfactory receptor neurons express a receptor that will interact with the same set of odorants.  All of the olfactory receptor neurons that express the same olfactory receptor, grow their axons and converge onto two bilaterally symmetrical glomeruli in the two olfactory bulbs. Glomerulus
  • 17.  Pyriform cortex sends inputs to medial dorsal thalamic nucleus.  Both pyriform cortex and medial dorsal thalamic nucleus are connected to the orbitofrontal cortex.  Entorhinal cortex is associated with hippocampal formation: declarative memory.  The olfactory signals can be important triggers for the recall of memory. Olfactory cortex
  • 18. Olfactory cortex sends inputs to the hypothalamus. In the hypothalamus odorants can engage our visceral motor systems. Olfactory cortex
  • 19. Pheromones are detected with special part of the olfactory epithelium and posterior part of the olfactory bulb: effect on motivated behavior in many mammals. How does this work in humans? Pheromones
  • 20. Olfactory function declines with age. Olfactory receptor neurons can regenerate after, for example, head trauma. Stem cells provide this ability. Functional recovery is never 100%.
  • 21. https://www.coursera.org/learn/medical- neuroscience/lecture: Leonard E. White, PhD, Duke University http://serendip.brynmawr.edu Literature