14 Olfaction 2012-1

Chemoreception

Nasal Chemoreception

(Smell)

GustationOlfaction

VomeronasalChemoreception

Chemesthesis(Trigeminal Chemoreception)

OralChemoreception

(Taste)

Chemesthesis(Trigeminal Chemoreception)

Introductory Neurobiology 2012

-receptor cells are neurons-long distance -chemesthesis refers to ability to detect irritating stimuli-vomeronasal requires contact w/stimuli; important for mammals, but not for primates

Olfaction, The Common Chemical Sense and

Vomeronasal Chemoreception



-nasal cavity is where we sense odors-two routes: sniffing directly through the nose or through the nasal cavity

Rodriguez. Nat. Neuro.(2003)

Chemosensory Systems in Mammalian Nose:

•Main Olfactory -general odorants

•Accessory Olfactory (Vomeronasal) -pheromones

•Trigeminal (Chemisthesis) -irritating/pungent volatiles



-pheromones are instinctual, but not entirely-detecting predators, aggressive displays, maternal behavior, finding mates, provides direct input to amygdala

Olfaction (Smell)


-hyposmia: reduced sense of smell-anosmia: no sense of smell; can have a general or specific (lose ability to smell specific odors)-cacosmia: having olfactory hallucinations [smelling things that aren't there]

The Importance of Olfaction


Our Sense of SmellCan really influence and alter our moodCan influence how long we stay in a roomSharpens our awareness of other people places and things.Can influence who we talk to and who we want to talk again (if histocompatability group is different, better chance of bonding)

• Can be a warning systemIntroductory Neurobiology 2012

Early warning system


“The Dogtor is in”(Pet Scans)

Moles-melanoma

Breast cancer

Lung cancer


-sense odor from body

Specificity and intensity of dog responses to breath/urine

99% accurate vs biopsies!


Flavor

BitterBitterSweetSweetSour Sour SaltySalty

Umami Umami (MSG)(MSG)


-majority of flavor is smell, predominantly retronasal smell-olfactory bulb in human is less than size of pinky nail

MemoriesMemoriesEmotionsEmotions


-olfactory memories are very strong -Several branches of olfactory nerve going to olfactory bulb -olfactory bulb provides direct input to the amygdala; also involves memory

Odor and Memories

Recall

Vision: 50% accurate after only 3 months

Smell: 65% accurate after a year


Structure of the Nose




-crib inform plate separates nasal cavity from brain; olfactory nerves terminate in olfactory epithelium-receptor cells are neurons-first synapse is in the brain; in olfactory bulb-neurons terminate in cilia

The Olfactory Epithelium

The nose is the gateway to the brain (problem if wacked in nose, can get brain infections; diseases by amebas get into nerve and go to brain)

Potential risks of trauma to the nose


Linda BuckIntroductory Neurobiology 2012

-cilia is where initial events in sensory transduction take place


-plate is very thin bone-neurons can regenerate, but there is a lot of scar tissue that can prevent neurons from going back to place


-first synapse is in olfactory bulb-neurons will go to glomerulus-there is a specificity in glomeruli


-pathway is from OE to OB to OC-sense of smell goes through cortex then the thalamus

Rodriguez. Nat. Neuro.(2003)

Transduction Mechanisms in Mammalian Nose


-g-protein is Golf-cAMP will open ion channel that allows Na and Ca to come in-Ca will open Cl channel to leave neuron to further depolarize-same tranduction pathways for smells, difference in receptor-~300 different receptors

The Olfactory Receptor Neuron


From: S. Ramon y Cajal y J.F. Tello y Muñoz. 1931



-when we stimulate neuron, we generate receptor potential-if receptor potential is sufficient, it will generate AP

A.~ 300B.~ 1, 000C.~ 10, 000D.~ 1 million

How many different odors can Humans discriminate?


Common Odors



Mechanisms of Olfactory Transduction



-each olfactory receptor expresses only one of the receptors

Olfactory Coding

Glomeruli



-there is coding by glomeruli-all same receptor cells send their axons to the same glomeruli-individual receptors tend to go to individual glomeruli


-receptor 1 responds to moer than one odor but respond to differnt intensity-coding is combination of labeled-line and cross fiber coding

Olfactory Receptor Genes

• Approximately 1000 genes in rodents

• Each olfactory receptor neuron expresses only 1 olfactory receptor

• These same receptors are expressed in the testis on sperm cells


Nobel Prize in Physiology or Medicine 2004

RICHARD AXEL LINDA BUCK

Protein must be able to detect a large number of odorants

One gene, multiple combinations (like immunity)

A large family of genes each encoding a different receptor

Discovered the Odorant Receptor Gene family (in 1991)


Odorant Receptor GenesHUGE gene family

Large fraction of our genome

Scattered throughout all of our chromosomes

Each odorant gene codes for a protein that is sensitive to a particular chemical structure(s)

• combinattion of receptors (1625)



-how single glomerulus receives axons from neurons expressing one receptor-one receptor one glomerulus


-similar receptors are not distributed randomly, located in zones-specificity of zonation for olfactory receptor neurons



-olfactory epithelium is like a mosaic of different receptor neurons expressing different individual receptors

* ~ 1000 OR types * One OR type per cell * Subset of OR types per zone * Zone to Zone projection * Cells of the same type project to a small number of fields (glomeruli) * Different odors activate different fields

Mori K. et al. Science (1999)



-shows convergence


-shows zone in olfactory epithelium and axons projecting to different glomeruli

Linda Buck


-4 receptor and odorants-multitude of combinations are possible-w/300 different receptors and 10000 different odors


-combinatorial coding is superimpozed on zonal label line coding

The Common Chemical Sense(Chemisthesis)

The importance of the common chemical sense


The Common Chemical Sense (Chemisthesis)

Receptors



-receptors for CCS are neurons; primary sensory neurons-form synapses in spinal cord


-trigeminal nerve is the fifth cranial nerve-burning sensation

The Common Chemical Sense (Chemisthesis)

Mechanism of transduction:

Activation of TRP channels


Trigeminal Chemoreception

Heat measured in Scovill units


TRP channels are located directly on trigeminal nerve


Trigeminal Ganglion Peripheral Nerve

Peripheral Terminal

Eye, Nose, or MouthACUTE TREATMENT

CHRONIC TREATMENT

NEONATAL TREATMENT

To Brain Stem

vanillyl alkyl chainaclyamide

Capsaicin desensitization


-if acute stimulation, nerve is stimulted-if chronic, nerve will become desensitized-if neonateal, nerve can be killed and not recover

Figure 3 VR1 responds to purified vanilloids and pepper extracts.. c, Responses to capsaicin (10 M) and extracts derived from four varieties of peppers in oocytes expressing VR1 (30 s application). Bottom right, relative potencies of each pepper extract are plotted (mean s.e.m., n = 3). Values were normalized in each cell to responses obtained with capsaicin (10 M). Extracts evoked no responses in water-injected cells. Reported pungencies for pepper varieties (in Scoville units) are: Habanero (H), 100,000–300,000; Thai green (T), 50,000–100,000; wax (W), 5,000–10,000; and Poblano verde (P), 1,000–1,500 (ref. 23). Capsaicin (C) is rated as 16x106 units.

From Caterina et al., Nature 389, 816 - 824 (23 Oct 1997) Introductory Neurobiology 2012

Relative “burn” of some common peppers

• Bell pepper 0• Jalapeño 2,000 - 5,000 units• Serrano 5,000 - 15,000 units• Thai 50,000 - 100,000 units• Habañero 100,000 - 300,000 units• Ghost pepper 1-3 million units!!!



Vanilloid receptor 1 (VR1)(TRPV1)

Vanilloid-like receptor 1 (VRL-1)(TRPV2)



-ligand-gated channel-capsaicin is fat-soluble-makes receptor open up at room temperature

Cool Receptors(TRPM8)



-TRPM8 responds to cold and menthol

TRPA1

• Mustard oil∀ ∆9-tetrahydrocannibinol

• Cinnamaldehyde



Stimulation of Nasal Trigeminal Fibers

• Associated with painful or irritating chemicals (tingling, stinging, burning)

• Examples of physiological reflexes– decreased respiration– increased nasal secretion– closure of nares and glottis– sneezing

• Effects of noxious stimulus is minimized and the individual is protected from further exposure


Vomeronasal Chemoreception and Pheromones


PheromonesDefinition: any chemical or set of chemicals produced by a living organism that transmits a message to other members of the same species.

Naive response, not learned

e.g. pups suckle, males fight, and estrus cycles are altered.

Their precise nature remains somewhat controversial

• males have more whisker growth


Invertebrate Pheromones

First discovered in silkworm moths

Females secrete a specific blend of odorants that is highly attractive to males

males fly upwind to find the source (as far away as a mile away)


Vertebrate Pheromones

Swabbed HamsterA male hamster swabbed with hamster pheromone (“Aphrodisin”) became sexually attractive to another male hamster


Bruce Effect

Male Urine can induce estrus (heat)

Bruce effect = odor memory

Same mouse: pregnancy maintained

New mouse or urine spike with pheromone: pregnancy terminated


The Importance of the Vomeronasal Organ (VNO)

and Pheromones

Mating behaviorTerritorial behaviorOther conspecific behavior



-VNO is located in pit in base of nose-goes to accessory olfactory bulb-projects to medial amygdala

Vomeronasal OrganSecondary Olfactory System

Sensory neurons synapse onto an Accessory Olfactory Bulb

Mouse: at base of nasal cavity

responds to bodily fluids introduced into the cavity (non-volatile)

The Pheromone detector?MOB detects pheromones as well

– terminate in microvilli


Mating Behavior

Anecdote about male hamster

Androstenone



Behaviors Mediated by Vomeronasal Organ and Main Olfactory Epithelium

From Mombaerts

•Aggressive behavior•Mating partner preference•Vocalizations•Endocrine effects (e.g. puberty delay, synchronization of estrous)

•Discrimination of general odors (instrumental conditioning, habituation/ dishabituation?)



Human Pheromones?

Anecdotal: man’s whisker growth faster in the presence of womenWomen who live together tend to get their period during the same time of the month. Chemicals collected from the armpit and dabbed under the nose have the same effect on women

One chemical will shorten the menstrual cycle by 1.7 daysAnother chemical will lengthen the cycle by 1.4 days


MHC

Major Histocompatibility ComplexIdentified as a major component in tissue graft rejection

Also appears to influence our body odor

Mechanism for detecting people with similar (or different) genotypes?


Human VNO?Human fetus

have a VNO

but connections appear to disappear after ~19 weeks of age

Adult: usually a depression (or pit) in nasal cavity

not always there or on both sides

most human VNO Receptors are pseudogenes... Introductory Neurobiology 2012

“When, from a long-distant past nothing remains,After the people are dead;after the things are broken and scattered.Still, alone, more fragile,but with more vitality,more insubstantial,but more persistent, more faithful,the smell and taste of things remain poised forever,like ghosts, ready to remind us…

Remembrance of Things Past––––Marcel Proust


14 Olfaction 2012-1

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