NEUROBIOLOGY B3

• Olfaction


  Our sense of smell
• Importance of sense of smell


  • As a remote sense of harmful substances or danger
  • Most smells not pleasant (~20%)
  • Test the edibility of food
  • Hedonistic value (pleasure)
  • Combines with taste to increase pleasure of eating food
  • Appetite and food choice
  • Drive to sustain = increased survival
  • Strong connections with limbic system (part of the brain controlling memory, emotions and behaviour)
  • Mode of communication (perfumes, pheromones)
• Many specific (airborne) chemicals evoke perception of distinct odours (other 'smells' are complex and involve numerous different compounds, e.g. cheese)
• Olfactory mucosa contains specialised neuroepithelium for olfaction
• Olfactory epithelium lines nasal and upper turbinates in nasal cavity
• Signal transduction mechanism in olfaction (GPCR)


  • Genes for ~1000 specific receptor proteins identified (<500 in humans, ~100-200 functional)
  • Binding of odorant molecule to receptor activates G-proteins
  • GTP coupled subunit stimulates adenylyl cyclase type III, increases cAMP
  • Open cyclic nucleotide gated cation channels, depolarisation and AP
  • Amplification by G proteins allow extremely low detection thresholds
• Olfactory receptor cells


  • Are "broadly tuned"
  • Each olfactory receptor neuron expresses a single membrane receptor protein
  • However, this coding is limited because many olfactory receptor neurons express olfactory receptors which can bind to the same set of odorants
  • Olfactory receptor neurons expressing the same protein are randomly dispersed throughout 'zones' within the olfactory epithelium
  • Single olfactory receptor neurons respond to a broad range of odorants
  • Odour discrimination is derived from a population code of neural activity
• Olfactory sensory neurons & glomeruli

  • Mammalian olfactory pathway involves massive convergence onto glomeruli
  • Same receptor classes in the epithelium project to the same glomerulus
  • Spatial distribution in olfactory bulb is strongly conserved
  • ~2000 olfactory glomeruli in each bulb (1-2 per receptor class: 2500 receptors/glomerulus)
  • Each glomerulus receives synaptic input exclusively from olfactory receptor neurons expressing the same receptor protein
  • Result is a spatial map within the olfactory bulb corresponding to activity in ~1000 different functional types of olfactory receptor neurons
• Interactions between glomeruli might reflect specific patterns of odour e.g. some odorant components in cheese versus bread activate different glomeruli
• Hence spatial pattern of glomerular activity is specific
• Olfactory processing within glomeruli

  • Local interneurons within glomeruli (periglomerular cells)
  • Inter-glomerular connections (granule cells, periglomerular cells)
  • Projection neurons to cortex (mitral cells, tufted cells) - also make lateral inhibitory connections with one another
• Activity in olfactory bulb

  • The olfactory bulb contains inhibitory interneurons, excitatory mitral and tufted relay neurons
  • Within each glomerulus, the dendrites of GABAergic periglomerular cells receive excitatory input and form reciprocal synapses with relay neurons suggesting a role in signal modification
  • The dendrites of GABAergic granule cells in the bulb have reciprocal excitatory-inhibitory synapses with secondary dendrites of the relay neurons - thought to provide negative feedback to relay neurons that shapes the odour response
  • Localised neural activity in olfactory bulb revealed through use of voltage sensitive (and Ca2+ sensitive dyes: in vivo imaging of activity of many neurons, stimulus specific activation of spatial pattern
  • Recent evidence suggest that neuronal encoding the glomeruli also use timing properties (oscillations and phase)
• Olfactory impairment


  • Varies enormously in normal (1000-fold sensitivity range)
  • Many people have specific anosmia's (up to 20% have a reduced ability to smell certain substances, genetic defects for specific receptors, COVID-19)
  • Impaired general olfactory ability (hyposmia) is common
  • Causes: upper respiratory tract infection, nasal obstruction (e.g. deviated septum), environmental pollutions (e.g. formaldehyde, smoking), head trauma (7% have lasting deficits), Parkinson's and Alzheimer's disease, prescription medications, age (loss of neurons beyond ~60 yrs.)
  • Can perceive irritant odours like ammonia or menthol (trigeminal nerve, another chemosensory pathway)
  • Abnormal odour perception (parosmia) in epileptics and schizophrenics
• Potential causes of anosmia from COVID-19

  • Damage from olfactory receptor neurons
  • Damage of sustentacular cells
  • Damage of the mitral cell
  • Utilisation of Zn by the virus prevents use of carbonic anhydrase
  • Increased mucous
• Projection of olfactory bulb neurons

  • Some projections to contralateral olfactory bulb
  • Part of the limbic system for emotional, behavioural, reflex components
  • Odour perception involves a large integrative and learned component
  • Projections to thalamus and then the orbitofrontal cortex
  • For conscious perception of smell orbitofrontal cortex integrates smell and taste signals for flavour perception
• Taste (gustatory system)


  • Olfaction detections airborne chemicals i.e. our sense of smell
  • Gustation detects signals in mouth i.e. our sense of taste
  • Sensory interactions e.g. taste of strawberry interacts with its smell, taste and texture on the tongue to produce flavour
• Importance of sense of taste

  • Enhances pleasure of food, appetite
  • Test the edibility of food (evolutionary value, many poisons are bitter, taste aversions, protective reflexes via unpleasant tastes)
  • GIT reflexes (salivation, digestive juices)
  • Homeostasis (salt consumption of deficient)
  • Gustation includes a large learned component, as with olfaction
• Taste buds


  • Taste receptor cells are modified epithelial cells (opposed to olfactory receptors which are CNS neurons)
  • 50-150 per taste cells per taste bud
  • Synapse with taste afferent nerve
  • Rapid turnover every 10-14 days
  • Declining numbers beyond age 45
• Taste sensations


  • There are 5 primary taste sensations (bitter, sour, sweet, salty, umami)
  • Highest sensitivity for substances taste bitter --> protective role
  • Genetic inability to taste some substances (e.g. phenylthiocarbamide, PTC in cabbage and broccoli)
  • Salt/sweet - tends to be detected anteriorly (umami)
  • Bitter tends to be more posterior, however distinction is not complete (no useful place code)
  • Taste detection and recognition are raised in the elderly (reduced olfaction, loss of taste receptor cells, prescription medications, reduced salivary flow)
  • Strategies: masking agents - sweet and salt tastants mask bitterness, flavour amplification, add food essences, MSG, switch between foods on plate to reduce taste receptor adaptation
• Taste receptor cells


  • Most taste receptor cells respond to more than one stimulus type
  • Single afferent nerves innervate multiple taste receptor cells, thus not strictly via labelled line (similar to smell)
  • Coding uses a population of broadly tuned neurons (learned pattern)
  • Tastant causes membrane potential change (graded receptor potential) in taste receptor cell
  • Salt and sour, after depolarisation, voltage-gated Ca2+ channels open, transmitter release
  • Sweet, bitter, umami --> 2nd messengers raise Ca2+, stimulating transmitter release, allows large amplification of weak signals
  • ~30 different receptor proteins identified for bitter compounds (key protective role)
• Taste receptors


  • Salty: ENaC
  • Sour: Otop1
  • Bitter: T2Rs
  • Sweet: T1R2 and T1R3
  • Umami: T1R1 and T1R3
• Projection of taste signals

  • Involves primary taste cortex (parietal cortex, insula deep within temporal lobes)
  • Primary taste afferent synapse in nucleus of solitary tract in medulla (integrating centre for signals + reflex generation, e.g. vomiting)
  • From there project to thalamus and relay to primary taste cortex
  • Projection to orbitofrontal cortex (temporal lobes) where information is integrated with olfactory (smell) and other sensory modalities to shape our conscious perception of 'flavour'
• Perception of flavour


  • Central integration of taste afferent signals with other sensations produces the perception of flavour e.g. block nose and eat onion, taste like apple (smell, touch, pain or irritation, temperature)
  • Subjects rendered anosmic have severely impaired flavour perception, even simple taste stimuli (salt, sugar) were reliant on smell for perception, some flavours could not be identified by any subject without the sense of smell (coffee, chocolate)
  • Substances which also activate 5th cranial nerve were less dependent on smell e.g. vinegar, whiskey
  • Much integration mediated via inputs from 'common' sensory pathway trigeminal nerve (5th cranial nerve)
• Olfactory Epithelium

  • Samples volatile substances from external air and oropharnyx
  • Sampled by olfactory sensory neurons
  • Mucosa allows compounds in solution to be distributed
  • Mucus allows for olfactory sensory neurons to not dry out and for compounds to be dissolved in mucus
  • Importance in flavour perception
• Bowman's gland produce mucus, which keep cilia from desiccating
• Olfactory sensory neurons have odorant receptors on their cilia membrane
• Olfactory sensory neurons project through bone into the olfactory bulb