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The Chemical Senses: Olfaction and Gustation — Vocabulary Flashcards

Learning Outcomes and Course Orientation

  • Be able to describe the specialized sense organs involved in olfaction/gustation at a molecular and cellular level.
  • Be able to describe how olfactory/gustatory information can be coded.
  • Be able to describe the structures of the brain that process this type of sensory information in the CNS.
  • Supporting texts: Neuroscience Purves 6th Edition; Principles of Neurobiology, Liqun Luo.

Sensory Systems: General Features

  • Sensory systems have multiple layers: Transduction → Encoding → Processing.
  • Energy types: light, chemical, mechanical.
  • General schematic: Receptor protein (Vision) → Cell membrane changes → Action potential; similar flow for Taste and Smell, Hearing, Balance, Touch.
  • Basic components: Sensory Receptor Cell, Sensory Neuron, leading to Sensation and Perception.
  • Key dimensions of sensation: Modality, Intensity, Duration, Location.

Functional Categories of Sensory Receptors

  • Exteroceptors (general and special) detect external stimuli.
  • General receptors include:
    • Mechanoreceptors: Superficial and Deep; slowly- and rapidly-adapting (Merkel's disc, Meissner's corpuscles, Ruffini's endings, Pacinian corpuscles).
    • Thermoreceptors: Warmth receptor, Cold receptor.
    • Proprioceptors.
    • Interoceptors.
  • Special receptors include:
    • Photoreceptors: Rods and cones in retina.
    • Mechanoreceptors: Hair cells in cochlea.
    • Chemoreceptors: Gustatory receptors, Olfactory receptors.
  • Other general categories listed include:
    • Baroreceptors, Glucoreceptors, Osmoreceptors, Nociceptors (thermal, mechanical, polymodal, silent nociceptors).
    • Golgi tendon organ, Muscle spindle, Joint capsule, Hair cells in otolith organs, Hair cells in semicircular canals.
  • Adapting vs non-adapting patterns summarized: slow/rapid adapting across modalities.

The Chemical Senses: Overview

  • Chemoreceptors are receptors that generate a signal when they bind chemicals in the external environment.

Olfaction: Distance Chemosensation

  • Thresholds vary between molecules:
    • Ethanol: 2\,\mathrm{mM}
    • 2-trans-6-cis nonadenial: 0.07\ \mathrm{nm}
  • Odour interpretation is concentration-dependent; e.g., Indole varies with concentration.
  • Natural odours are composites: they consist of combinations of different molecules.
  • Olfaction reflects the pattern of activation across different olfactory cells (across-fibre pattern coding), interpreted by higher CNS centers.

Olfaction: Sensory Receptors Location

  • Sensory receptors are located in the olfactory epithelium.
  • Olfactory afferent fibres project directly to the olfactory bulb in the CNS.

The Olfactory Epithelium: Structure and Turnover

  • Olfactory neurons are bipolar and unmyelinated sensory afferents.
  • Specialised cilia are embedded within a mucus layer; mucus concentrates chemicals and brings them into contact with the cilia.
  • Mucus layer is produced by Bowman's glands.
  • Olfactory neurons have a high turnover rate: they are prone to damage and last ~6–8 weeks.

How Odours Are Transduced

  • Odour detection involves stimulation of olfactory cilia; stimulation of olfactory soma also observed.
  • Experiments determining odorant receptor locations showed cilia are highly sensitive to odours.

Odour Receptors: Nobel Prize and GPCRs

  • Nobel Prize (2004) awarded to Richard Axel and Linda Buck for discovery of odorant receptors as GPCRs.
  • Odorant receptor (OR) genes are a large gene family:
    • 3–5% of the human genome are OR genes (largest gene family).
  • Gene counts:
    • Humans: ~400 odorant receptor genes.
    • Dogs: ~1000 odorant receptor genes.
    • Mice: ~1200 odorant receptor genes.
  • Each olfactory receptor neuron (ORN) expresses exactly one receptor gene.
  • The OR genes are evolutionarily conserved among species, supporting their role in smell detection.
  • Large sequence variability among ORs enables detection of a vast range of chemicals.

Odorant Receptor Gene Expression and Spatial Distribution

  • Distribution patterns of odorant receptor gene expression observed in the olfactory epithelium: several labeled patterns (A, B, C, D) show receptor neuron distribution and glomerular targeting.
  • Olfactory receptor neurons expressing the same odorant receptor gene project to the same glomerulus in the olfactory bulb, ensuring convergence by receptor type.

Odorant-Sensitive GPCRs in Cilia and Signaling Pathways

  • Odorant receptors expressed in cilia couple to a signaling cascade:
    • Passive depolarisation via Adenylyl Cyclase III (ACIII, \mathrm{A}\mathrm{C}_{\mathrm{III}}) producing cyclic nucleotides.
    • Activation of cyclic nucleotide-gated (CNG) ion channels.
  • Experimental verification of this signaling cascade performed using genetically modified mouse strains.

Nasal Epithelium: Receptor Neurons and Transduction Details

  • The nasal epithelium houses the bipolar olfactory receptor neurons (ORNs).
  • Olfactory receptor proteins are concentrated in the cilia of ORNs.
  • Individual ORN genes show selective distribution in the nasal epithelium.
  • Odorant molecules bind to GPCRs, triggering a cyclic nucleotide-gated (CNG) channel activation.
  • This leads to a graded receptor potential that passively spreads to the initial segment of the afferent axon, reaching threshold to trigger an action potential.
  • The olfactory receptor signals pass through the cribriform plate and enter the olfactory bulb.

Central Processing: The Olfactory System at a Glance

  • Major target of the lateral olfactory tract in humans is the piriform cortex.
  • The thalamus is involved as a relay in olfactory processing, though olfaction is unique among senses in its relatively direct cortical routing.

Olfactory Bulb: Receptors, Glomeruli, and Amplification

  • Olfactory receptor neurons expressing the same odorant receptor converge onto the same (ipsilateral and contralateral) glomeruli in the olfactory bulb (OB).
  • The OB contains glomeruli, mitral cells, and interneurons forming a neural network:
    • Olfactory receptor neurons project to glomeruli.
    • Mitral cells form the main output of the OB, sending signals to higher brain regions via the olfactory tract.
  • Each glomerulus receives input from ORNs expressing the same receptor type.
  • A single glomerulus can contain up to ~25 mitral cells and ~25,000 olfactory receptor neuron inputs.
  • Mitral cell axons project from the OB to the accessory olfactory nuclei and elsewhere, contributing to the broader olfactory network.
  • Convergence of signals on glomeruli serves to amplify weak signals and integrate inputs across many ORNs.

Molecular Encoding and Electrical Patterns in the OB

  • The relationship between a receptor type and its glomerulus enables distinct regions of the OB to respond to different chemicals.
  • Odours activate unique spatial patterns in the OB depending on chemical composition.
  • In experiments, odorants and glomerular responses are quantified by changes in fluorescence (ΔF/F):
    • Example: Percent change in response for specific odorants (e.g., 1-octan-3-ol, hexane, isoamyl acetate) shows chemically distinct single odorants maximally activate one or a few glomeruli.
    • Represented as: \Delta F / F with odorant-dependent amplitudes.

Across-Fibre Pattern Coding: How Odors Are Represented

  • Individual ORNs are broadly tuned rather than perfectly specific:
    • An alcohol molecule with varying chain length elicits responses from multiple sensory neurons.
    • Different neurons respond best to different alcohols; their response patterns across neurons define the odor.
  • A small population of neurons can discriminate odors via their collective activity patterns:
    • With only three sensory neurons, some discrimination is possible due to the unique combination of firing across neurons.
    • Central neurons read the across-fiber pattern to identify the odor, a mechanism termed across-fibre pattern coding.
  • Experimental illustration: Changing molecule length of alcohol alters which neurons respond and how strongly; the overall pattern across the population discriminates the odor.
  • Naturally occurring odors (banana, lemon, cheese, bread) activate broad populations of neurons; no single neuron is exclusively tied to one chemical.
    • Some neurons respond strongly, some weakly, some not at all to a given natural odor.
    • This approach helps define the odorant spectrum each neuron responds to.
  • Concentration dependence also modulates responses to odors like indole, further shaping across-fibre patterns.
  • Conclusion: Odour identity is encoded by across-fibre patterns across many sensory neurons, not by a one-to-one mapping.

Mapping of Odorants in the Olfactory Bulb: Glomerular Convergence

  • Olfactory receptor neurons expressing the same receptor protein send axons to the same glomerulus, creating a spatial map in the OB that is odorant-specific.
  • Different molecular components in a complex odor activate a distinctive population of glomerular neurons, reinforcing the idea of a spatial olfactory map in the OB.
  • It is not fully understood how this activity is organized in higher-order centers such as the piriform cortex, since there is no simple topographic map like in touch.

The Olfactory System: Spatial Maps and Higher-Order Processing

  • A spatial map exists in the olfactory bulb (glomerular map) corresponding to odorant receptor types.
  • Higher-order processing in the piriform cortex involves interpreting the olfactory bulb activity; unlike other senses, the piriform cortex does not preserve a straightforward, regionally organized map of odors.
  • The system appears to rely on combinatorial patterns across many neurons to represent odors rather than a single, dedicated pathway per odorant.

Central Processing and Pathways

  • The lateral olfactory tract projects primarily to the piriform cortex (primary olfactory cortex).
  • The pathway involves relay through the olfactory bulb to higher cortical areas; the thalamus acts as a relay or modulatory node in olfactory pathways, distinguishing olfaction from other senses that relay first through the thalamus.
  • The piriform cortex processes odor identity and perhaps olfactory perceptual quality, integrating olfactory information with memory and emotion via connections to limbic structures.

Summary: Smell Encoding and Implications

  • Most olfactory neurons can respond to more than one odor molecule.
  • An odor is coded by the activity pattern across many sensory neurons (across-fibre coding).
  • This coding strategy allows a rich and high-dimensional representation of odors using a relatively small set of receptors.
  • Learning outcomes recap:
    • Describe specialized olfactory structures at molecular and cellular levels (epithelium, ORNs, cilia, Bowman's glands, mucus).
    • Describe how olfactory information is encoded (GPCR signaling, cAMP/CNG cascade, receptor potentials, action potentials, and across-fibre coding).
    • Describe brain structures processing olfactory information (olfactory epithelium, olfactory bulb with glomeruli and mitral cells, piriform cortex, and thalamic relationships).
  • Practical and philosophical implications:
    • The olfactory system relies on a combinatorial, distributed code that offers vast receptor diversity and robust odor discrimination, but its higher-order cortical organization remains less well understood than other sensory systems.
    • The genetic diversity of odorant receptors underpins individual and species-specific differences in odor perception.
    • The reliance on across-fibre coding suggests that perceptual odor identity arises from population activity rather than single-receptor-carrier signals, with implications for designing artificial olfactory systems and understanding sensory perception in health and disease.