Transcript The Olfactory System

The Chemical Senses
The olfactory system is one member of the chemical senses. The other two are taste and the
general chemical sense. Although we won’t cover these in this course, you should at least
know a bit about them.
Taste is transduced by receptor cells within taste buds on the tongue (primarily). These cells
express a family of receptor proteins that bind families of molecules representing the standard
taste categories: salt, bitter, sweet, sour and unami (glutamate). The receptor cells activate
nerves that project to the medulla.
The general chemical sense is transduced by unmyelinated somatosensory afferents present
in the mouth; these are what is activated by capsaicin (hot pepper ingredient); activating
these receptors on the skin would lead to a sensation of pain and heat. Activating them on the
tongue leads to the sensation of “hot peppers” and is interpreted as a taste.
The Olfactory System- Vomeronasal Organ
Bear et al.
As I mentioned earlier, all senses process
communication and environmental stimuli in
separate channels. This separation is found at
very high cortical levels in the auditory and visual
system. There is an exceptionally clear division of
labour at the very beginning of the olfactory
system. Olfactory receptors are found at two
sites in the nose: the olfactory epithelium (dorsal
nasal cavity) and the vomeronasal organ (small
pits of receptor cells on either side of the nasal
septum).
The vomeronasal organ has receptors that bind
pheremones- chemicals released from the body
and used to convey messages related to
reproduction and territory. The pheremonal
receptors are members of a gene family distinct
from those for general olfactory stimuli.
The vomeronasal organ is innervated by its own
neurons that project to the accessory olfactory
bulb; this in turn has its own targets in the brain
devoted to olfactory communication, reproduction
etc. This sense system has not been thoroughly
studied and we will not deal with it any further in
this course.
The Olfactory System: Receptors 1
Olfactory receptors are located in a layer of support cells;
they project their “dendrites” into the mucosa (where odorants
are trapped) and their axons through a thin bone to terminate
in the olfactory bulb (part of the CNS).
Different receptors respond to different odors and these
receptors are spatially segregated to some degree on the
olfactory epithelium.
Bear et al.
The Olfactory System: Receptors 2
There are, in the rat, about 1000 odorant receptor genes. Each olfactory receptor
expresses only one of these genes. This is the first critical feature of olfactory coding.
When an odorant binds to the olfactory receptor protein it stimulates a G-protein that
activates adenylate cyclase; cAMP binds to and opens channels permeable to Na+/Ca2+
and Cl- channels. The resulting current flow depolarizes the receptor cell (receptor potential)
causing it to spike. Its axon terminal in the OB then releases transmitter (glutamate) to
excite the target mitral cells.
Bear et al.
The Olfactory System: Olfactory Bulb 1
Bear et al.
Olfactory receptor axons terminate on mitral
cell dendrites in a restricted encapsulated
structure called a glomerulus; a glomerulus
contains the dendritic bush of one mitral cell but
many olfactory receptor axons. All the OR
axons ending in one glomerulus contain are
So each mitral cell codes for one kind of
from receptors expressing same olfactory
odorant molecule. This is the primary basis
binding protein.
of olfactory coding.
The Olfactory System: Olfactory Bulb 2
Left: Optical imaging demonstrates
different parts of the OB are activated by
different odorants.
Right: Electrical recording demonstrates
that the same odorant causes different
patterns of spiking in different olfactory
neurons (locust).
It appears likely that the code for
odorant identity is spatio-temporal:
an odorant will activate different but
overlapping populations of OB neurons
and the activated cells will have different
patterns of spiking discharge.
Bear et al.
The Olfactory System: Olfactory Cortex
The precise odorant responses of OB mitral cells is lost.
The OB has an extensive and
complex set of projections. One
major target is the olfactory cortex.
Bear et al.
Olfactory cortex contains pyramidal cells that receive excitatory
(glutamate) synaptic input from OB mitral cells. Each mitral
cell axon ends on many PCs. The PCs project out of olfactory
cortex. But they also have collaterals that project locally to
many other PCs (excitatory- glutamate). The synapses onto
the PCs use NMDA receptors and are plastic (LTP). Why?
1.
Many objects emit numerous volatile odorants (banana,
>100).
2.
An animal cannot predict which it will encounter so it must
learn to recognize the different combinations of odorants
associated with different objects (e.g. bananas vs fish).
3.
Perhaps the plastic synapses in olfactory cortex are part of
this learning process; they might permit the animal to learn a
combinatorial code and thus recognize different odor emitting
objects: olfactory pattern recognition.
Population Response to Odorants
Yaksi, 2009
The olfactory cortex (lateral pallium) is situated on the ventral aspect of the telencephalon and
not readily accessible for recording in vivo.
In fish the equivalent telencephalic region is called Dp and is at the surface.
Yaksi et al using two photon confocal Ca2+ imaging to investigate the response of Dp neurons
to different odorants (zebrafish). Different subpopulations of Dp neurons respond to different
amino acids presented to the nose of the fish.
The population response to natural odorants (from whatever zebrafish eat or from whatever
eats zebrafish) is not known.
How to analyze such population responses is not known and is a major problem in
Systems/Theoretical Neuroscience.
Temporal Response to Odorants
Stopfer, 2003
Neurons in the locust change their response as the odorant changes or due to changes in the
concentration of a single odorant. It would seem that the locust would not be able to
discriminate changes in concentration versus changes in odorant.
However when the change in response over time (trajectory) is examined the overall shape of
the response is maintained with changes in concentration. But different odorants produce
different trajectories.
The methods to do this kind of analysis are very sophisticated and still under development
The Olfactory System: Peripheral Stem Cells
Beites et al.
Olfactory receptor cells are constantly turned over. The source is
stem cells within the olfactory epithelium. This is a highly
regulated process and is being used as a model of neuronal stem
cell biology. The axons of new ORNs penetrate into the OB.
Special glial cells (ensheathing) facilitate this; ordinary adult glia
block axonal regeneration; so the ensheathing cells are of
interest to molecular neuroscientists interested in axonal
regeneration. Further, the new ORN axons make correct
connections in the OB: that is, to the glomerulus specified by the
receptor type they express. The mechanism for such specific
regeneration is unknown and also of intense interest.
The Olfactory System: Central Stem Cells
Stem cells within the subventricular zone of the
lateral ventricles generate new neurons that
migrate into the OB where they mature into a
type of inhibitory interneuron (granule cell).
These GCs integrate themselves into the OB
circuitry. The control of migration and synapse
formation of new neurons in the adult brain is
an important topic for those interested in
treatment of stroke etc.
What is the role of newly generated OB granule
cells?
An enriched odor environment leads to
increased survival of new granule cells (but
no increase in proliferation). This is
correlated with an improvement in olfactory
memory.
Saghatelyan et al.