sensory systems lecture 3 -chemoreceptors

what is olfaction

a sensory system that enable organisms to interact with and understand their environment 

what are the vital functions of olfaction

locate edible items, detecting threats and identifying potential mates

what are the evolutionary purposes of olfaction

navigation and chemical sampling

what are odorants

specific chemical compounds that are capable of eliciting an olfactory response- activates olfactory receptor- tends to be volatile

what are characteristics of odorants

volatile, lipophilic organic compounds with high diversity and high structural variability

what is an odour

combination of multiple odorants

what is the initial site of odour detection?

the olfactory (nasal) epithelium

what is the olfactory (nasal) epithelium

specialised tissue lining the nasal cavity

what are olfactory sensory neurons (OSNs)

specialised neurons in the olfactory epithelium that detect odorants and convert chemical signals into electrical signals 

where do OSN dendrites project

into the mucus-filled olfactory epithelium

what specialised structures are found on OSN dendrites

Cilia, whihc contain olfactory receptors responsible for detecting odour molecules

what is the function of the cilia on olfactory sensory neurons?

they are primary sites of transduction, converting chemical (odorant) signals into electrical signals 

where do the axons of olfactory sensory neurons project?

directly to the olfactory bulb, the first. processing centre for smell in the brain

what is the function of basal cells in the olfactory system

they are stem cells that regerate olfactory sensory neurons; located at the base of the epithelium 

what is the fucntion of supporting (sustentacular ) cells?

they are glial-like cells that provide structural and metabolic support to OSNs

describe the structure of an olfactory sensory neuron

it has a dendrite with cilia extending into the mucus layer and an axon projecting to the olfactory bulb

what is the role of the mucus layer in the olfactory epithelium

it covers the epithelium and dissolves odorant molecules , allowing them to reach the olfactory receptors

what is the olfactory bulb and its function?

the olfactory bulb is the first brain region that receives and processes olfactory information from OSNs

what is the fundamental principle of the odorant detection mechanism

the fundamental principle is the conversion of the chemical signal from an odorant into an electrical signal (action potential) that the brain can interpret

why is detecting odourants in the mucus layer challenging

odourants are typically hydrophobic, yet they must function in the aqueous mucus layer, requiring specialised transport mechanisms 

what role does the binding protein play in odor detection?

it binds hydrophobic odourants in the mucus and transports them to olfactory receptors; it has a pocket where the odourant sits

what is the odourant itself?

the chemical molecule being detected by olfactory receptors

what is the receptor in odour detection?

a protein embedded in the OSN membrane that specifically binds to odourants and initiates signal transduction

what does a modifying enzyme do in olfactory mucus

it can chemically modify odourants, altering their activity or receptor binding

what is the role of a degrading enzyme in the olfactory system

it breaks down odourants to terminate the signal and ensure the system reflects the current environment 

what is the function of the mucus in the olfactory epithelium

it provides an aqueous medium for odourants to dissolve and interact with binding proteins and receptors

what is the cytosol in this context

the intracellular fluid where downstream signalling occurs after receptor activation

what family of receptors do olfactory receptors belong to?

the G-protein coupled receptors ( GPCRs) family

how many times do GCPRs span the plasma membrane

seven times ( they have seven transmembrane domains)

what part of a GPCR binds the ligand

the extracellular portion binds a specific ligand such as an odourant

what binds to the intracellular portion of a GPCR

a G-protein trimer (composed of alpha, beta and gamma subunits)

in the resting state, what is the Ga subunit bound to

Guanosine Diphosphate (GDP)

what happens when a ligand binds to a GPCR

the receptor changes conformation, causing GDP-GTP exchange on Ga which then dissociates from the Gby dimer

what happens after the G-protein subunits dissociate?

both Ga-GTP and Gby activate downstream effector proteins, triggering intracellular signalling pathways

what specific G-protein is used in olfactory signalling

Gaolf, a Ga subunit specialised for olfactory neurons

what is the resting state of Gaolf

it is bound to GDP and associated with B and y subunits, forming an inactive heterodimer

what happens when an odourant binds to an olfactory GPCR

the receptor changes shape, causing GDP-GTP exchange on Gaolf and dissociation of the G-protein complex

what enzyme does Gaolf-GTP activate

Adenylate cyclase (ACIII), specific to olfactory neurons

what does adenylate cyclase (ACIII) do in this pathway

it converts ATP to cyclic AMP (cAMP), which acts a secondary messenger

what effect dies the rise is cAMP have inside the cell

it opens cyclic nucleotide-gated (CNG) ion channels allowing Na+ and Ca2+ influx and Cl- efflex

what is the result of ion channel activation in OSNs

the membrane depolarises, generating an action potential that transmits the odour signal to the brain

summarise the sequence of events in olfactory transduction

Odorant binds → GPCR (olfactory receptor) activates → Gαolf exchanges GDP for GTP → activates ACIII → ATP → cAMP → opens CNG & Ca²⁺-activated Cl⁻ channels → action potential generated.

what causes the increase in cAMP concentration in olfactory sensory neurons?

GPCR activation (via odorant binding) activates adenylate cyclase which converts ATP to cAMP

what effect does increased cAMP have on the olfactory sensory neuron

it opens specific ion channels, leading to depolarisation and generation of an electrical signal 

what activates cyclic nucleotide-gated channels (CNGCs)

they are directly activated by cAMP

what ions flow through CNGCs when they open

Na+ , Ca2+ ion enter the neuron (cation influx)

what happens to CNGCs in the absense of cAMP

they remain closed

how does CNGC activation affect the membrane potential

the influx of positive ions depolarises the membrane, moving it toward the threshold for an action potential

what is the additional role of Ca2+ influx through CNGCs

the increase in intracellular Ca2+ activated Ca2+-gated chloride channels CaCCs

what activates CaCCs (Ca²⁺-gated chloride channels)

the rise in intracellular Ca2+ caused by CNGC activity

what is the ion movement through CaCCs (Ca²⁺-gated chloride channels)

Cl- ions flow out of the neuron (Cl- efflux)

why does Cl- efflux cause depolarisation instead of hyperpolarisation

olfactory neurons have a high intracellular Cl- concentration, so Cl- efflux make the inside more positive, enhancing depolarisation

What is the overall effect of Cl⁻ efflux on the odor signal?

It amplifies depolarization, creating a stronger odor signal even for low odorant concentrations.

Why is this mechanism unusual compared to most neurons?

Normally, Ca²⁺-activated Cl⁻ channels cause hyperpolarization, but in olfactory neurons, they further depolarize the cell.

why must the odourant signal be terminated

to ensure that the olfactory system can respond to new stimuli and prevent continuous overstimulation

what is calmodulin CaM

A Ca²⁺-binding regulatory protein that helps terminate the olfactory signal.

How does CaM contribute to signal termination?

• Inhibits CNGCs, reducing Na⁺/Ca²⁺ influx

• Activates PDEs, breaking down cAMP

• Activates CaMKII, deactivating adenylate cyclase

What is the effect of CaM directly inhibiting CNGCs?

It reduces cation influx, promoting repolarization of the neuron.

What do PDEs do in olfactory neurons? (phosphodiesterases)

Hydrolyze cAMP into AMP, lowering cAMP levels.

How are PDEs activated?

By Ca²⁺-calmodulin (CaM).

What happens when PDEs reduce cAMP concentration?

CNGCs close, stopping ion influx and helping end the signal

What activates CaMKII in olfactory neurons? (Calcium/Calmodulin-Dependent Kinase II)

Ca2+ bound to calmodulin CaM

what is the role of CaMKII in odourant signal termination (Calcium/Calmodulin-Dependent Kinase II)

it deactivates adenylate cyclase, reducing further cAMP production

Summarize how the odorant signal is terminated.

Ca²⁺ influx → activates CaM →
• inhibits CNGCs → stops ion influx
• activates PDE → degrades cAMP → closes channels
• activates CaMKII → deactivates adenylate cyclase
→ Neuron repolarizes and resets for next odorant

Where does the olfactory signal originate?

In the dendrites of olfactory sensory neurons located in the olfactory epithelium.

Through which structure do olfactory sensory neuron axons pass to reach the brain?

They pass through small perforations in the cribriform plate of the ethmoid bone.

Where do olfactory sensory neuron axons synapse?

They synapse with mitral and tufted cells in the olfactory bulb.

What is the olfactory tract composed of?

The axons of mitral and tufted cells.

Approximately how many odorants can humans detect and discriminate?

Humans can detect around 10⁵ and discriminate about 10³ odorants.

What type of receptors are odorant receptors?

G-protein Coupled Receptors (GPCRs).

How many odorant receptor genes are in the human genome?

About 1,000, forming one of the largest gene families.

What strategy allows humans to detect many odors with few receptor genes?

The combinatorial coding strategy.

What does the combinatorial coding strategy mean?

Each receptor detects multiple odorants, and each odorant activates a unique pattern of receptors.

What effect does odorant concentration have on receptor activation?

It changes which receptors are activated and how strongly, influencing perception.

What are GPCRs responsible for in the olfactory system?

They detect odorants in the nasal mucus layer.

What helps transport hydrophobic odorants to olfactory sensory neurons?

Odorant binding proteins.

What is the key pathway leading to OSN depolarization?

Odorant → GPCR → Gαolf → Adenylate cyclase → cAMP → cation (CNG) channels → Depolarization + Cl⁻ amplification.

What does the “one-neuron-one-receptor” rule mean?

Each mature olfactory sensory neuron expresses only one receptor gene type.

What experimental technique visualizes olfactory receptor neuron distribution?

Transgenic Lac-Z reporter mice using β-galactosidase staining.

How are neurons expressing the same receptor organized in the bulb?

Their axons converge on two specific glomeruli in the olfactory bulb.

What is an odour map?

A spatial pattern of glomeruli activity representing specific odours.

Where is the vomeronasal organ (VNO) located?

On the bottom surface of the nasal epithelium.

What is the primary function of the vomeronasal organ?

Detection of pheromones related to social and sexual behaviour.

Do humans have a functional vomeronasal organ?

Its existence and function in adults are debated; it may be vestigial or non functional

What is the Flehmen response?

A behaviour in animals that allows pheromones to enter the VNO for detection.

Where do VNO ( vomeronasal sensory neurons ) project?

To the accessory olfactory bulb, then to the hypothalamus.

What receptor families are involved in pheromone detection?

V1r and V2r GPCR families.

What behaviours do V1r and V2r receptors mediate? and what are these receptors sensitive to?

Aggression, social interactions, and sexual behaviours. pheromones found in urine and bodily fluids

What is TRP2 channel

A calcium ion channel crucial for vomeronasal signal transduction

What happens in TRP2 knockout (TRP2–) mice?

they show no pheromone-induced aggression, though mounting and vocalization may still occur.

What do TRP2 knockout studies demonstrate?

TRP2 is essential for pheromone-driven aggression, linking VNO signaling to innate behaviour.