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Chapter 2: The Chemical Senses
• Olfaction and gestation are chemical senses, where information is extracted from the environment by
direct chemical interactions. Molecules interact with receptors in the nose of mouth, generating neural
• Smell is a distance sense: chemical molecules are wafted to the nose olfactory chemoreceptors by
atmospheric currents, so the stimulating substance can be quite remote.
• Taste is a contact sense: chemical molecules need to be in solution directly contacting chemoreceptors.
• Other chemical senses include interoception in the kidney, pancreas, gut, brain etc. to control the
concentration of sodium, pH, glucose and amino acids in the body. The reception of neurotransmitters
and hormones is also technically chemoreception.
• Odours can be used to detect prey and predators, identify mates or competitors, and judge the
palatability of food. Even humans can distinguish gender by breath, hand, or armpit smell, and women
may synchronize menstrual cycles due to chemical
• Odours are very effective at evoking powerful
emotional responses and memories.
Anatomy & Physiology of Smell
• The olfactory system is remarkable for its ability to
signal the presence of just a few aromatic molecules,
and to discriminate between thousands of different
• Olfaction can be divided into orthonasal olfaction
and retronasal olfaction.
• The vomeronasal perception system is related,
though separate from the olfactory epithelium, and
detects pheromones in certain animals. It is unclear
whether humans have this system.
• The nose must balance its job of filtering the air for lungs, and channelling air with molecules onto the
olfactory epithelium for smelling.
• Olfactory sensory neurons (OSNs) are found in the roof of the nasal cavity, on the olfactory
epithelium. This area of 2-4 square centimeters contains about 6 million receptors. Olfactory receptor
cells are constantly renewed, with a lifespan of 60 days (2 months).
• The olfactory epithelium doesn’t just contain OSNs. It also contains supporting cells that provide
metabolic and physical support for OSNs and produce mucus, as well as basal cells which are OSN
• The receptor proteins are located on cilia which project from the dendrites of each OSN, into the
olfactory mucosa. Each cell has about 5-40 cilia.
• The mucus is mostly water. Chemical molecules must be dissolved in the olfactory mucus to arrive and
activate the receptors on the cilia; hydrophobic chemicals need to bind with odorant binding proteins.
• Olfactory receptor proteins bind the odorants, and are typically GPCRs. It takes 7-8 odour molecules
bound to initiate an action potential. Page 43-57, 14 pages Page 2 of7
• There are 500-1000 different receptor protein types in humans, each activated by different odour
molecules. Each receptor responds to multiple odorants, and a single odorant excites multiple receptors.
• The olfactory mucosa also contains free nerve endings, which mediate sensations of coolness,
tingling, and burning that arise from high concentrations of chemicals.
• Olfactory sensory neurons are different from other sensory receptor cells:
o They are in direct contact with both the outside world and the brain.
o Insufflation by sniffing in substances is a way to get substances to the brain, without being
blocked by the blood-brain barrier. Some drugs are applied this way.
o Contrast with visual receptors protected by eye layers, hearing receptors protected by eardrum
and outer ear, and taste buds
buried in papillae
Sensory Pathways & Cortical Processing
• The axon of each receptor cell passes
through the cribriform plate, a
perforated bony plate in the skull at the
level of the eybrows, to project to a
specific mitral cell in the olfactory
• The olfactory bulb is a blueberry-sized
extension of the brain cortex. There are
two olfactory bulbs, one in each
hemisphere corresponding to the left
and right nostrils. Connections are
ipsilateral rather than contralateral.
• The synapses between receptor cell
axons and mitral cell dendrites bundle
together to form olfactory glomeruli.
Several thousand receptors connect to 5-25 cells in each glomerulus.
• Cranial nerve I, the Olfactory Nerve consists of the axons of the OSNs, which move through the
cribiform to the mitral cells. This is a short, but also very thin and thus very slow nerve – takes longer to
perceive odours than other senses.
• The different receptor cell types are distributed randomly
about the olfactory epithelium, but the glomeruli to which they
project are at identical anatomical positions in different animal
• The axons of the mitral cells travel to the rest of the brain
along the olfactory tract.
• This projects to the primary olfactory cortex directly without
stopping at the thalamus (unique among senses, reflective of
its ancient origin); there is also direct projection to the
• When receptors in one nostril are stimulated, there is bilateral
cortical activation; for other senses, cortical responses are
typically lateralized. However, there is asymmetry with most
coding and processing done in the right hemisphere.
• There is also processing in the hypothalamus, entorhinal cortex, and hippocampus.
• Conscious perception of smell involves signals from the primary cortex to the orbitofrontal cortex, via
the thalamus. Consciousness of smells tends to be lower as the thalamus is not implicated as early on. Page 43-57, 14 pages Page 3 of 7
• Since receptor activation is modulated by breathing, so is cortical activity of olfactory processing.
• Detectability varies with odour: some chemicals are detectable at concentrations thousands of times
weaker than others.
• Humans are particularly sensitive to musk (0.00007μg/L), and to merceptan (added to gas to make
leaks detectable), but much less sensitive to methyl salicylate (wintergreen, 100 μg/L).
• Women have lower detection thresholds than men, especially during ovulation – but not during
• By age 85, 50% of population is effectively anosmic.
• At detection threshold, a subject’s ability to recognize an odour is usually poor. Recognition rates
improve as concentration of substance increases.
• Women tend to perform better than men, in 65 out of 80 tested odours, e.g. coconut, fruit gum, band-
aid, cat food. Men identified odours of ammonia, Brut aftershave, and sherry better.
• Olfactory preferences are learned, not innate.
• One linking proposition for receptor activity to odour recognition
is that each smell is specific for each receptor, and activation of
that receptor allows perception of the associated smell. However,
we recognize thousands of different odours with only 500-1000
receptor types – there are too few receptors for this to be true,
and most odorants are a cocktail of many molecules.
• Each receptor can respond to multiple odours, and each odour
activates multiple receptors. Thus each odour chemical likely
comprises a combination of molecular features, which are used
across many molecules.
• Each odour produces a different pattern of activity across the
receptor type, a combinatorial receptor code for odour. This
theory is an example of population coding, where stimulus
response is carried in the responses of a whole population of
• We have good perceptual organization: each smell is a large
composition of volatile chemicals, yet we can even decompose the smells of a variety of substances to
• The mitral cell distribution is consistent among many species. Recognition of a particular substance
thus derives from recognition of a certain spatial pattern of activity across different mitral cells in the
• The perceived intensity of a smell drops by 30% of more after continual exposure. When the smell is
removed, and then presented only briefly over the next time period, its apparent intensity climbed back to
pre-adaptation levels. Both adaptation and recovery rates are exponential. Smell is essentially a
• This can occur by receptor adaptation, where after continual exposure receptors stop responding (e.g.
downregulation) to the odorant, and thus detection ceases.
• This can also occur by cognitive habituation, where after long-term exposure there is psychological
habituation – the receptors are still stimulated, but we ignore it on the cognitive level by modifying our
perception. E.g. Certain smells from our own body (cigarette smoke for smokers),or from a specific Page 43-57, 14 pages Page 4 of 7
environment like our room. Adaptation ensures they become undetectable, as it would serve little
purpose to be continually reminded of them.
• Odour adaptation is selective – exposure to a specific odorant raises thresholds only for odorants with
similar smells. Additionally, adaptation has much larger effects for self-adaptation, than for cross-
adaptation of a related smell which activates the same receptor(s).
Memory & Identification
• Our sense of smell is very durable, after several days, months, or years. This is especially so for smells
connected to an emotional event with processing in the amygdala.
• Attaching a verbal label to a smell is not easy, even for a familiar odourant: tip-of-the-nose
phenomenon. One does not have lexical access to the name of the odorant, as language and olfactory
perception are quite disconnected. There are fewer words for experience of smells compared to other
• This disconnection may be because olfactory information is not integrated in the thalamus prior to
cortex processing. As well, olfaction is lateralized in the right hemisphere, while language is lateralized in
• Anosmia: Odour blindness, with partial anosmia being inability to detect a specific odour. For example,
1 in 10 are insensitive to cyanide, and 1 in 1000 to butyl mercaptan. These specific anosmias are
genetically transmitted, reflecting a deficiency in a specific type of olfactory receptor molecule.
• Total anosmia may occur from sinus illness or head trauma – a hard blow to the head can cause the
cribriform plate to be jarred back or fractured, slicing off the fragile olfactory neurons.
How good is the human sense of smell?
• The filter and olfactory functions of the nose work against each other. Since we are bipedal, our nose is
farther from the ground, so our nose can be smaller as we don’t need as much filtering power. This
reduces the size of our olfactory epithelium and the number of OSNs.
• How does our sense of smell compare? Dogs and rats are better with some molecules, but primates
are better with others.
• The retronasal olfaction role in flavour is important with the advent of hum