Olfaction Flashcards
What are the very general stages of perception in sensory systems?
Receptor activation > Detection > Transduction > Encoding of info > Conscious perception
What are the 3 chemical senses?
Taste
Smell
Detection of pheromones
What are the 2 olfactory pathways in mammals (maybe in humans, maybe not…)
Accessory olfactory pathway (Vomeronasal pathway) and main olfactory pathway
True or false: the VNO and MOE pathways are distinct units
False: there is a lot of overlap between the 2 pathways
Describe the human main olfactory bulb
It is much smaller than other mammal olfactory bulbs
Describe the very general pathway of the mammalian/human main olfactory system
Sensory cells in the main olfactory epithelium project through the cribiform plate to the main olfactory bulb, where they synapse to glomeruli, then in the glomerulus synapse to mitral cells, signals are then transmitted to higher processing areas of the brain
True or false: an single odour is produced by the perception of a discrete chemical compound
False: an odour = a plume of many different odorant compounds
Describe the chemical properties of an effective odorant
Should be a small molecule which is volatile
Odorants can be grouped these 2 ways
By chemical structure/type and by concentration
What are 4 requirements of the olfactory system?
- Sensitivity (discriminate between strengths)
- Integration (e.g. odorant plume)
- Discrimination (perception and identification of different odorants)
- Memory of different odorants
The sensory neurons from the MOE project to…
The main olfactory bulb (MOB)
The synapse between cells in the MOE to the MOB occurs in…
The glomeruli
Where are glomeruli located?
In the olfactory bulb
In the rodent olfactory system, where are the olfactory receptors located? (where in the cell)
On the cilia of the olfactory neurons of the MOE
The “relay centres” of the olfactory system are the…
Glomeruli
Define anosmia
Loss of smell
More common than complete anosmia is..
Partial anosmia, the loss of certain smells
Partial anosmia may be an indicator of these diseases (2)
Parkinson’s and Alzheimer’s
Partial anosmias are common with these kinds of odors
Musk odors
Normal, gradual loss of smell as a person ages is associated with a decrease in…
Apetite
In some COVID patients whose smell does not return, what is the cause of this anosmia?
Loss of supporting olfactory cells (“supporting cells”) which normally help nourish and support OSNs
In some COVID patients whose smell does not return, what is the cause of this anosmia?
Loss of supporting olfactory cells (“supporting cells”) which normally help nourish and support OSNs
True or false: the olfactory system transmits information via action potentials
True
What kind of neurons are OSNs based on the structure classifications of neurons (unipolar/bipolar/multipolar)
Bipolar
Who were the 2 scientists who shared the Nobel prize for the identification of olfactory receptors
Buck and Axel
What were the 3 hypotheses about olfactory receptors that Buck and Axel had?
- GPCRs
- Receptor gene family must be large and diverse
- Expression of receptors will be restricted to the olfactory epithelium
How did Buck and Axel go about trying to find olfactory receptors?
Designed a primer for a TM region of a GPCR which is common to many GPCRs and used RT-PCR on the MOE
If all GPCRs are roughly the same length, how did Axel and Buck design a system which would be able to indicate if they had found a multigene family?
Added Hinf1: cuts at a specific sequence common in GPCRs
First column: Hinf1 Fragments add up to 700 bp
2nd column: Hinf1 fragments add up to wayyy more than 700 bp: probably found a multigene family!
In olfactory neurons, how many kinds of olfactory receptors are present?
In general: one receptor type per neuron!
If olfactory receptors had not been GPCRs, would Axel and Buck have been successful in their experimental design? Why not?
No, because they were looking for a highly conserved region of GPCRs, and other types of receptors don’t necessarily share structural homology the same way GPCRs do
Are olfactory receptors exclusive to the main olfactory epithelium?
Mostly in the olfactory system but they exist outside of this also
Which of Axel and Buck’s original 3 hypotheses about olfactory receptors turned out not to be entirely true?
Olfactory receptors are only in the olfactory system: some are elsewhere
What receptor families of olfactory receptors are present in the vomeronasal system?
V1Rs and V2Rs
What are the 5 classes of olfactory receptors?
- Olfactory receptors (in the MOE)
- V1Rs (VNO)
- V2Rs (VNO)
- Trace amine-associated receptors (TAARS, MOE)
- Formyl peptide receptors
Describe combinatorial coding in olfactory receptors
An odorant activates a particular set of olfactory receptors: this encodes a distinct signal for each odor
What is the advantage of combinatorial coding?
Uses fewer receptors to get more specificity
In olfactory receptors, a single receptor recognizes (single/multiple) odorants
Multiple
In olfactory receptors, a single odorant is recognized by (single/multiple) receptors
Multiple
After the synapse at the glomerulus, the main output neuron of olfactory information is…
Mitral cells
What are the key interneurons of the olfactory system?
Periglomerular cells and granule cells
The periglomerular and granule cells are analogous to these cells in the visual system
Horizontal and amacrine cells
Describe the organization of the MOE and MOB
There is zone to zone projection: receptors
are organized into zones of glomeruli which respond to similar stimuli
What is the average life span of OSNs?
30-60 days
Are OSNs replaced throughout life, or post-mitotic?
Replaced throughout life
The stem cells which replace OSNs are called…
Basal cells
Axons of like OSNs terminate in…
The same glomerulus
The more abundant kind of interneuron in the olfactory system is the…
Granule cell
Describe why the glomeruli are the signal processing centers of the olfactory system
Synapse happens there, input from interneurons (lateral inhibition) happens at glomerulus
True or false: glomeruli participate in cross-talk to modify signals
True
Where are the 2 zones of neurogenesis in the adult brain?
- Subventricular zone of the lateral ventricles
- Subgranular zone of the dentate gyrus
Both in the hippocampus!
Cells born in the subventricular zone migrate (directionally) to this area of the brain
Rostrally to the olfactory bulb
Describe birth dating of olfactory neurons
Inject BrdU into cells and detect using BrdU sensitive antibody
BrdU labels cells in S-phase
Can observe where they migrate into the brain
When a nare was blocked (sensory deprivation), how did the number of BrdU-positive cells change compared to the unblocked nare of a mouse?
Fewer BrdU-positive cells in the blocked nare: sensory input increases OSN production
Similar molecules tend to activate glomeruli which are…
Near each other
What kind of synapses occur in the olfactory system which is uncommon elsewhere in the nervous system
Dendrodendritic synapses
Dendrodendritic synapses in the olfactory system occur between these cell types
Mitral and granule cells
GABA acts on these channels in mitral cells, opening them and causing this result
Cl- channels, causing influx of chloride causing hyperpolarization: this inhibits firing of neighbouring cells to increase acuity
In a study by Sousy et al (2009), SpH mice (fluorescent pH-sensitive imaging tool) were examined. What were the main findings? (2)
- Glomeruli map which react to similar odorants are reliably placed across animals
- There is a local diversity in sensory tuning
Cells which have different classes of olfactory receptors also differ in this way
Have unique transcriptomes! Cells clearly reacting in response to odorants in unique ways
Each OSN having a unique transcriptome may be useful for this developmental process
Axon pathfinding
What are the final destinations for the newborn cells of the SVZ?
Will become granule and periglomerular cells
Do granule and periglomerular cells express olfactory receptors?
No
How does an increase in granule cells affect olfactory discrimination of highly similar odorants?
Granule cells synapse between mitral cells (lateral inhibition)
When there are more granule cells, neighbouring mitral cells are more silenced when a central granule cell is active: better acuity
What are the 2 lesser-known branches of the olfactory system
The gruenberg ganglion and the septal organ of masera
What are the 2 classes of pheromone signals discussed in this course
Primers and releasers
V1Rs use this kind of G protein
Galpha i2
V2Rs use this kind of G protein
Galpha o
How many V1R receptors have been found in humans?
5
How many V2R receptors have been found in humans?
None
Where are human V1Rs expressed?
In the MOE
In mice, (V1R/V2Rs) are closer to the lumen
V1Rs closer to lumen
The first ligand to be indentified for the VNO neurons was…
2-heptanone
Do humans have a VNO?
No
V2R are coexpressed with these molecules
MHC class Ib
The proposed reason why V2Rs and MHC molecules are coexpressed is…
Why do we think this?
MHC might bind different immune-related ligands and aid in signalling of V2Rs in some way
Think this because MHC are expressed in dendritic tips
Which MHC receptors have been located near the dendritic tips of VNO olfactory neurons
M1 and M10 - think they have a role in the detection of pheromones
What is the one difference in the signal transduction cascade between V1Rs and V2Rs?
Use different G-proteins
V1R: Gai2
V2R: Gao
Describe the general projections of the cells in the VNO
- VNO neurons project to AOB glomeruli
- In glomerulus, neurons synapse to mitral cells
- Mitral cells project to the vomeronasal amygdala
Describe the ordering of glomeruli in the AOS
Not quite as ordered as the main olfactory system
Describe the projection organ to organ of the vomeronasal system
VNO > AOB > Amygdala > Hypothalamus
Describe the projection organ to organ of the main olfactory system
MOE > MOB > Piriform cortex + friends > Thalamus
Other than the piriform cortex, the MOB also makes some connections to…
The amygdala
Other than the thalamus, the piriform cortex also makes projections to…
The hypothalamus
What of the 5 tastes are aversive?
Sour, salty, and bitter
What is the key nutrient being detected by “sour” neurons
Protons (H+)
True or false: the tongue has an intrinsic taste map
False
Name the different coloured areas of papillae
Red: Circumvallate papilla (singular!)
Green: Foliate papillae
Purple: Fungiform papillae
