Olfactory System
The Chemical Senses
Lecture Overview
Lectures conducted by Dr. James Dillon (jcd@soton.ac.uk)
Lecture 1: Smell (Olfaction)
Lecture 2: Taste (Gustation)
Learning Outcomes:
Be able to describe the specialized sense organs involved in olfaction and gustation at a molecular and cellular level.
Be able to describe how olfactory and gustatory information can be coded.
Be able to describe the structures of the brain that process this type of sensory information in the Central Nervous System (CNS).
Supporting Text:
Neuroscience by Purves et al., and Principles of Neurobiology by Liqun Luo.
Sensory Systems: General Features
General characteristics of sensory systems include:
Multiple layers involved in the processing of sensory information.
Different types of energy stimuli (Light, Chemical, Mechanical) that sensory systems respond to.
Components of sensory systems:
Transduction: The conversion of physical stimulus to electrical signals.
Encoding: The representation of sensory stimulus information in a recognizable form.
Processing: The interpretation of encoded information leading to perception.
Types of Sensation and Perception include:
Vision, Taste, Smell, Hearing, Balance, Touch.
Functional Categories of Sensory Receptors
Sensory receptors can be categorized based on their location and function:
Exteroceptors: Respond to external stimuli (e.g., vision, hearing).
Proprioceptors: Monitor body position and movement.
Interoceptors: Respond to stimuli from within the body (e.g., hunger).
General types of receptors include:
Mechanoreceptors: Respond to mechanical stimuli.
Photoreceptors: Detect light (rods and cones in the retina).
Chemoreceptors: Respond to chemical stimuli (gustatory and olfactory receptors).
Thermoreceptors: Respond to temperature changes.
Nociceptors: Detect pain (thermal, mechanical, polymodal).
The Chemical Senses
Chemoreceptors: These are specialized receptors that generate a signal when they bind to chemicals in the external environment. This form of sensory perception is thought to be evolutionarily conserved from lower organisms (e.g., C. elegans, Drosophila) through to higher organisms like mammals.
Olfaction: Refers to the sense of smell, specifically information derived from airborne molecules known as odorants.
Gustation: Refers to the sense of taste, specifically information derived from chemical and physical qualities of ingested substances.
Roles in Behavior:
Lower organisms utilize these senses for seeking food and avoiding toxic substances, while higher organisms benefit from stimulating the gastrointestinal system and evaluating the nutritional value of food sources.
Olfaction: Distance Chemosensation
The threshold for odor detection varies between different molecules:
Example: Ethanol threshold is 2 mM and 2-trans-6-cis nonadenial threshold is 0.07 nM.
The interpretation of a smell can be concentration-dependent, e.g., indole.
Natural odors typically comprise a combination of different molecules.
Olfactory perception is linked to the pattern of different olfactory receptor cells activated by various molecules, known as across-fibre pattern coding. This pattern is interpreted at higher centers in the CNS.
Olfactory Epithelium
Sensory receptors for olfaction are located in the olfactory epithelium.
Olfactory afferent fibers project directly to the olfactory bulb in the CNS.
Olfactory Neurons:
Have a bipolar configuration and are unmyelinated sensory afferent neurons.
Specialized cilia embedded within a mucus layer concentrate chemicals to enhance contact with odorants.
Mucus is produced by Bowman's glands.
These neurons are prone to damage and have a lifespan of 6-8 weeks.
Odor Transduction Mechanism
Initial stimulation occurs at the olfactory cilia, leading to neuronal activation.
Research on the location of odorant receptors has pointed towards the sensitivity of cilia to odorants.
In 2004, Richard Axel and Linda Buck were awarded the Nobel Prize for their work on odorant receptors, specifically the role of G-protein coupled receptors (GPCRs). Main points include:
GPCRs are part of the largest gene family in humans, constituting about 3-5% of the genome.
There are approximately 400 functional odorant genes in humans, with more in dogs (1000) and mice (1200).
Each olfactory receptor neuron (ORN) expresses only one type of receptor gene, allowing for a vast array of odor detection based on the sequence variability of the GPCRs.
Distribution of Odorant Receptor Gene Expression
Experimental expression of olfactory receptor neurons can be visualized using specific markers such as olfactory marker protein (OMP).
Examples of distribution studies:
A) Neurons labeled in green (using OMP).
B) OMP-GFP transgene distribution in nasal epithelium of an adult mouse.
C) Specific I7 odorant receptor distribution.
D) Specific M71 odorant receptor distribution.
Olfactory Signal Transduction Pathway
When an odorant binds to a GPCR in cilia, the following molecular mechanisms are activated:
Passive depolarization occurs within the cilia.
Activation of Adenylyl Cyclase III (ACIII) produces cAMP from ATP.
The cAMP then activates cyclic nucleotide-gated (CNG) ion channels.
The graded generator potential spreads to the afferent axon segment, triggering an action potential once the threshold is reached.
Olfactory processing continues as the receptor axons pass through the cribriform plate to the olfactory bulb.
Molecular Encoding and Electrical Patterns
Each individual ORN is sensitive to a subset of odor molecules, with distinct patterns of action potentials generated in response to specific stimuli.
Experimental findings:
Membrane current responses are generated by different odorants over time, indicating differentiated responses across various neurons.
Example substances in testing:
Cineole, Isoamyl acetate, and Acetophenone.
Neurons demonstrated varied activation based on time of exposure to stimulus, confirming the responses are nuanced across different types of odorants.
Across-Fibre Pattern Coding
The coding mechanisms for odor discrimination can involve manipulating chemical structures.
Testing on alcohols demonstrates the relationship between molecular structure length and sensory neuron activation:
Responses from three sensory neurons plotted vs. alcohol molecule lengths indicate varying sensitivity and specificity of apertures for action potentials in response to different alcohols.
The combined activity patterns of multiple sensory neurons underpin the identification of specific odors, emphasizing a complex interplay that describes each unique scent via across-fibre pattern coding.
Discrimination of Naturally Occurring Odors
Research includes testing naturally occurring substances such as banana, lemon, cheese, and bread on sensory receptors to isolate their activating effects.
Findings indicate:
Each sensory neuron detects a range of substances, and the degree of response varies significantly.
This exploration helps to narrow down the potential odorants that a neuron may react to, enhancing our understanding of olfactory encoding, particularly in concentration dependence, exemplified by responses to indole.
The Olfactory Bulb and Neural Processing
Structure and arrangement:
Mitral Cells: Project from the olfactory bulb into the olfactory tract.
Convergence and amplification occur at bilayered glomeruli where similar receptor neurons converge, enhancing the signal.
Each glomerulus can receive input from up to 25 mitral cells and 25,000 olfactory cells.
The relationship between a specific type of odorant neuron and its corresponding glomeruli enables distinct regions of the olfactory bulb to respond differentially to various chemicals.
Olfactory Signal Mapping and Organization in the CNS
The interaction between odors and glomeruli allows for a distinctive spatial pattern in the olfactory bulb:
This reflects the chemical composition of the odors processed.
This spatial differentiation aids in central processing, with the major target for the lateral olfactory tract being the Piriform Cortex.
Unlike other sensory systems that have clear spatial maps, olfactory processing does not exhibit a straightforward spatial representation, highlighting a unique complexity in olfactory information processing.
Summary of Olfactory Encoding
Key takeaways from olfactory system processing:
Most olfactory neurons can respond to multiple odor molecules.
Odors are encoded by action patterns from many sensory neurons (across-fibre pattern coding).
ORNs expressing similar proteins project to the same glomeruli, amplifying the signal detection.
The diverse molecular components activate unique sets of glomerular neurons, facilitating spatial mapping of odors in the olfactory bulb.
The olfactory bulb transmits information to the piriform cortex and thalamus, where further processing occurs without a clear mapping akin to other sensory systems, emphasizing the complexity of olfactory encoding and perception.
The Chemical Senses
Chemoreceptors: These are specialized sensory receptors that generate a neural signal upon binding to chemical substances in the external environment. This sense is considered evolutionarily conserved, indicating its fundamental importance in survival from simpler organisms like C. elegans and Drosophila to more complex species such as mammals. These receptors are essential for various behaviors including foraging and mate selection.
Olfaction: The sense of smell, or olfaction, enables organisms to detect and interpret airborne chemical molecules known as odorants. It plays a critical role in behaviors such as seeking food, identifying potential dangers (like smoke or decay), and even social interactions through pheromones.
Gustation: The sense of taste, or gustation, pertains to the detection of chemical and physical properties of ingested substances. Taste is vital for assessing food quality and ensuring nutritional intake, distinguishing between sweet (energy-rich), bitter (potentially toxic), salty, sour (indicating possible spoilage), and umami (savory) flavors, coordinated through specific receptors that bind to various taste molecules.
Roles in Behavior: In lower organisms, chemoreception is crucial for survival; these senses help in locating food sources and avoiding toxins. In mammals, they are significant not only for dietary choices but also for social and reproductive interactions, impacting behaviors governed by scent cues and flavor preferences.
Olfaction: Distance Chemosensation
The ability to detect odors varies across different substances based on their molecular composition and concentration. For example, the detection threshold of ethanol is approximately 2 mM, while it is merely 0.07 nM for 2-trans-6-cis nonadenial, illustrating the significant differences in sensitivity.
The perception of a smell may be concentration-dependent, meaning that a molecule might be perceived differently at varying concentrations, further complicated by the complex olfactory mixture of natural odors.
Olfactory perception relies on the activation of a diverse array of olfactory receptor cells, a process known as across-fibre pattern coding. This entails a specific ensemble of receptor activations that is interpreted by higher brain centers, contributing to the richness of olfactory experiences.
Olfactory Epithelium
Sensory receptors related to olfaction are embedded in the olfactory epithelium, a specialized tissue located in the nasal cavity. Olfactory afferent fibers transmit sensory information directly to the olfactory bulb, a critical region in the Central Nervous System (CNS).
Olfactory Neurons: These neurons exhibit a bipolar structure and lack myelination, which means they are unmyelinated sensory afferent neurons. The specialized cilia of these neurons are coated in a mucus layer which not only enhances chemical concentration but is also produced by Bowman's glands.
Notably, these neurons exhibit a relatively short lifespan of 6-8 weeks and are susceptible to damage from environmental factors, highlighting the importance of continuous regeneration in maintaining olfactory function.
Odor Transduction Mechanism
The process begins when odorants bind to receptors located on the olfactory cilia, initiating neuronal activation. Recent research has highlighted the specific role of G-protein coupled receptors (GPCRs) in this mechanism.
In awarding the Nobel Prize to Richard Axel and Linda Buck in 2004, their research underscored that GPCRs form the largest gene family in the human genome, composing approximately 3-5% of it. Humans possess around 400 functional odorant receptor genes, while other species like dogs and mice have significantly more, enhancing their olfactory capabilities.
Distribution of Odorant Receptor Gene Expression
The expression of olfactory receptor neurons can be visualized using markers such as olfactory marker protein (OMP).
Examples of distribution studies include the visualization of neurons labeled with markers and the expression patterns of specific odorant receptors like I7 and M71 in the nasal epithelium of adult mice.
Olfactory Signal Transduction Pathway
When an odorant binds to a GPCR on olfactory cilia, this binding triggers a sequence of molecular events:
Passive depolarization within the cilia is initiated.
Activation of Adenylyl Cyclase III (ACIII), which in turn catalyzes the conversion of ATP to cAMP.
The generated cAMP opens cyclic nucleotide-gated (CNG) ion channels, leading to a graded potential that triggers action potentials in the afferent axons once the depolarization threshold is met.
Following this, olfactory processing continues as the receptor axons traverse the cribriform plate to reach the olfactory bulb, underscoring the cascade of cellular and molecular interactions involved.
Molecular Encoding and Electrical Patterns
Each olfactory receptor neuron (ORN) is selective to a subset of odor molecules, generating distinct patterns of action potentials in response to particular stimuli.
Experimental observations indicate that membrane ion current responses vary over time with different odorants, revealing nuanced and specific neuronal responses across the olfactory bulb.
Example substances tested in such experiments include cineole and isoamyl acetate, emphasizing the complexity and variability of olfactory processing.
Across-Fibre Pattern Coding
Odor discrimination mechanisms involve the manipulation of chemical structures at the receptor sites.
Tests involving alcohol demonstrate a direct correlation between molecular chain length and sensory neuron responses, reinforcing the notion that sensory neuron specificity and sensitivity can vary in relation to molecular characteristics.
The comprehensive activity patterns across multiple sensory neurons allow for a complex encoding of specific odors through across-fibre pattern coding, crucial for differentiating scents.
Discrimination of Naturally Occurring Odors
Investigative research on naturally occurring substances, like banana and lemon, assesses how different chemicals activate sensory receptors and isolate responses by each neuron.
Findings reveal significant variability in the degree of neuronal response among different odorants, shedding light on olfactory encoding and the concentration-dependent nature of responses, as illustrated with indole.
The Olfactory Bulb and Neural Processing
In terms of structure, mitral cells are responsible for transmitting signals from the olfactory bulb through the olfactory tract, engaging in significant convergence and amplification processes at bilayered glomeruli where similar receptor neuron signals converge, thus enhancing olfactory signaling.
Each olfactory glomerulus can integrate inputs from numerous mitral cells and thousands of olfactory sensory neurons, emphasizing a unique organization conducive to complex odor processing.
Olfactory Signal Mapping and Organization in the CNS
The interaction of odors at the glomeruli fosters distinctive spatial patterns in the olfactory bulb, which correspond to the chemical profiles of the processed odors.
The major output from the olfactory bulb targets the piriform cortex where further signal processing occurs, contributing to olfactory perception.
Unlike other sensory modalities that possess straightforward spatial representations, olfactory processing exhibits intricate complexity, integral to understanding the nature of olfactory coding.
Summary of Olfactory Encoding
Key insights regarding olfactory system processing:
Olfactory neurons exhibit multisensory response capabilities, able to respond to varied odor molecules.
Odors are represented through action patterns from a collective group of sensory neurons, demonstrating the principle of across-fibre pattern coding.
Olfactory receptor neurons expressing similar proteins also project to corresponding glomeruli, amplifying signal detection.
Diverse molecular properties activate distinct sets of glomerular neurons, enabling specialized odor mappings within the olfactory bulb.
The olfactory bulb forwards sensory information to the piriform cortex and thalamus, where complex processing occurs without clear mapping, highlighting the distinctive nature of olfactory encoding and perception in comparison to other senses.