1. Domina Petric, MD
Olfaction

2. Olfactory pathway
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.

3. 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.

4. Targets of the olfactory bulb (the olfactory cortex):
Axons of
the mitral
cells make
lateral
olfactory
tract.
Pyriform cortex and entorhinal cortex
are cortex structures
(laminar cell organisation).
Olfactory bulb
Targets of the olfactory bulb (the olfactory cortex):
Pyriform cortex
Olfactory tubercle
Amygdala
Entorhinal cortex
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.
Primary axons are
first cranial nerve.
Olfactory receptors
Entorhinal cortex is associated
with hippocampal formation.

5. 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.

6. Amygdala Anatomy Olfactory bulb Lateral olfactory tract Olfactory
tubercle
Pyriform
cortex
Amygdala

7. Olfaction
There is no obligatory thalamic relay between the olfactory bulb and olfactory cortex.
There is no known map of the sensory environment.

8. Sensory transduction in the olfactory epithelium
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.

9. Sensory transduction
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.

10. 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).

11. 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).

12. 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.

13. Combinatorial olfactory code
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).

14. Combinatorial olfactory code
Same odorant molecule can interact with more than one receptor depending upon the geometrical configuration of odorant molecule.

15. Glomerulus
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.

16. Glomerulus
Glomeruli are the first site of synaptic connection between the olfactory epithelium and the brain.
Each glomerulus recieves input from about olfactory receptor neurons.
All of these 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.

17. Olfactory cortex
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.

18. Olfactory cortex
Olfactory cortex sends inputs to the hypothalamus.
In the hypothalamus odorants can engage our visceral motor systems.

19. How does this work in humans?
Pheromones
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?

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%.
Olfactory function declines with age.

21. Literature
Leonard E. White, PhD, Duke University