The Chemical Senses

1. 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 Chemical Senses

2. The Olfactory System- Vomeronasal Organ As I mentioned earlier, all senses process communication and environmental stimuliin 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. Bear et al.

3. 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.

4. 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.

5. 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 from receptors expressing same olfactory binding protein. So each mitral cell codes for one kind of odorant molecule. This is the primary basis of olfactory coding.

6. 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.

7. The precise odorant responses of OB mitral cells is lost. The Olfactory System: Olfactory Cortex 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? Many objects emit numerous volatile odorants (banana, >100). 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). 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. The OB has an extensive and complex set of projections. One major target is the olfactory cortex. Bear et al.

8. 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.

9. 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

10. 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.

11. 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.