Olfaction L12

Brief overview

• Humans can detect hundreds of thousands of odors, though only ~20% are pleasant.

• We can discriminate between ~16,000 distinct odors.

Where does odourant detection occur

• posterior of the nose in the olfactory epithelium (OE)

• Olfactory sensory neurons in OE project via olfactory nerve to olfactory bulb

Anatomy of Olfactory detection

Olfactory Epithelium (OE)

• Located at the back of the nasal cavity.

• Contains three main cell types:

  1. Olfactory receptor cells (ORNs) – carry out transduction; have axons that enter CNS; about 6–10 million in humans.

  2. Supporting cells – glia-like; secrete mucus, antibodies, and odorant-binding proteins.

  3. Basal cells – stem cells for regenerating ORNs (~4–6 week cycle).

Vomeronasal Organ (VNO)

• Present in most mammals.

• Specialized for detecting pheromones.

• Projects to the accessory olfactory bulb, then to amygdala and hypothalamus.

• Removal disrupts pheromone signaling, not general odor detection.

Olfactory Epithelium (OE)

• Located at the back of the nasal cavity.

• Contains three main cell types:

  1. Olfactory receptor neurons (ORNs) – carry out transduction; have axons that enter CNS; about 6–10 million in humans.

  2. Supporting cells – glia-like; secrete mucus, antibodies, and odorant-binding proteins.

  3. Basal cells – stem cells for regenerating ORNs (~4–6 week cycle).

Vomeronasal Organ (VNO)

• Present in most mammals.

• Specialized for detecting pheromones.

• Projects to the accessory olfactory bulb, then to amygdala and hypothalamus.

• Removal disrupts pheromone signaling, not general odor detection.

How does Odour Detection in relation to Molecular Basis work

• Odourants interact with specific receptors in the olfactory cilia and dendritic knob.

Odourant Receptors (ORs)

• Discovered by Buck & Axel, 1991.

• ~1000 genes in vertebrates code for ORs (GPCRs – G-Protein Coupled Receptors).

• Each ORN expresses only one receptor gene (allelic exclusion).

• ORNs expressing the same receptor are scattered but confined to spatial zones in the OE.

Signal Transduction

• ORs activate a G-protein called Golf, which triggers intracellular signaling upon odorant binding.

• Leads to depolarization and signal sent to the olfactory bulb.

Organisation of the Olfactory Bulb

• ORN axons expressing the same receptor converge on 1-3 glomeruli in the olfactory bulb.

• Glomeruli are functionally specific – each processes input from ORNs with the same receptor.

• Synapses form with mitral cells, which relay signals deeper into the brain.

Simplified version

• (ORNs) that detect the same kind of smell all send their signals to the same 1-3 glomeruli.

• In the glomeruli, these signals connect to mitral cells, which then pass the information on to other parts of the brain for further processing.

How is Mapping and Visualization achieved

• Genetic tools (e.g., Tau-lacZ) are used to map OR expression and axon projections.

• Expression of Tau-lacZ under a specific OR promoter highlights the projection of ORNs to specific glomeruli.

• This confirms that the olfactory system maintains a spatial map of receptor input.

How is Regeneration and Specificity achieved

• ORNs regenerate regularly and re-establish connections with the same glomeruli.

• OR gene expression is required for correct targeting—receptor protein guides axons to the right glomerulus.

• Substituting receptors alters glomerular targeting, indicating combinatorial targeting mechanisms.

What is the Neural Coding of Odors

• Despite only ~1000 receptor types, we detect many more odors via:

  • Population coding: Each odor activates multiple broadly-tuned receptors.

  • Spatial coding: Specific patterns of glomerular activation represent different odors.

• Odor identity is encoded in combinatorial patterns of receptor and glomerular activity.

Neural coding of smell (8)

– there are ~1000 different olfactory receptor genes

– each olfactory neuron expresses one receptor gene

– all neurons expressing the same receptor gene project to only 1-3 glomeruli in the olfactory bulb

– thus, each glomerulus responds only to the chemicals that activate a specific receptor

• However, we can differentiate between more than 16000 odours. How?

– Population coding

• receptors broadly tuned

• each odorant stimulates a different population of receptor

What is Odour Representations and Imaging

• Intrinsic optical imaging and genetic labeling are used to visualize glomerular activation.

• Different odorants produce distinct spatial activity patterns.

What are Trace Amine-Associated Receptors (TAARs)

• Involved in detecting ethologically relevant odors.

  • TAAR4: Detects predator odor (e.g., lion urine); knockout mice show no aversion.

  • TAAR5: Responds to trimethylamine (sex pheromone in male mice); knockout mice lack attraction.

What are 4 Key Experiments and Concepts

• Buck & Axel (1991) – discovered odorant receptor gene family.

• Jones & Reed (1989) – identified Golf as a key signal transduction molecule.

• Wang et al. (1998) – showed ORs are required for correct axon targeting.

• Mombaerts et al. (1996) – visualized ORN projections using tau-lacZ reporters.