The Chemosensory System MEDS 5371 Spring 2012 Royce Mohan, PhD

Our wondrous chemosensory system

So how do we choose odorants for perfumes?

Penguins use odor-based perception for monogamous relationship for life At the nesting sites in March, there is intense competition between the females for a mate followed by a necessarily brief courtship. After a single egg is laid the females return to the sea for many months. This leaves the males to incubate the eggs in the bitter cold until females return only when the chicks begin to hatch. Ah, so many choices! My mom and dad wear Solo per Te

The ChemoSensory System: the Nose

The olfactory epithelium

Odorant receptor proteins

Structure of odorant receptor

Molecular mechanisms of odorant transduction Olfactory transduction starts with odorant binding to the GPCR and involves second messengers and ionic currents Very strong adaptation to smells – one of the senses that is strongly or fast adapting

Responses of receptor neurons to selected odorants The optimal odorant is very difficult to find. Hence, the science of the perfume industry is still an art. $30 Billion in revenues!

Organization of the mammalian olfactory bulb Mitral, tufted cell dendrites in glomerulus; axons to pyriform cortex, amygdala, entorhinal cortex Reinnervate the glomerulus; specific for 1 receptor type Axons grow through cribriform plate Neurons replaced every few weeks Olfactory receptors here; cilia up to 30  m long

Inputs; much “sharpening” of signal here; mitral cell tufts = dendrites Output to cortex interneurons MANY glomeruli / mitral cell; MANY Mitral cells/glomerulus 100 intrinsic neurons (periglomerular, granule) = interneurons / mitral or tufted cell 1,000 ORN inputs/ mitral/tufted cell 25,000 ORN inputs/ glomerulus Organization of the mammalian olfactory bulb

ORs are widely distributed in the OE Olfactory sensory neurons converge on a single glomerulus OB Transgenic mouse nasal cavity and brain showing olfactory epithelium (OE) and olfactory bulb (OB) from a single olfactory receptor (OR) receptor labeled with lacZ and stained with X-gal OE Cribriform plate

55 receptor genes respond to octanol One gene expressed per OSN – pseudogenes [no AUG start; premature STOPs] initially expressed, replaced by functional one Humans have about 340 functional olfactory receptor genes, on many chromosomes, in clusters (families) Expression of receptor genes around olfactory epithelium is stochastic – not topographic by place in epithelium Characteristics of OR genes

Concentration dependent effects

Why is my air freshener smelling like celery? oc ta n ol

Hexanol Hexanoic acid Heptanoic acid Octanoic acid Nonanoic acid ODOR Heptanol Octanol Nonanol Rancid, sour, goat-like Rancid, sour, sweaty Rancid, sour, repulsive waxy, cheese, nut-like Sweet, violet, woody Sweet, rose, orange Fresh, rose, oily floral Sweet, herbal, woody ODORANT

Odor coding in the olfactory epithelium (OE) and olfactory bulb (OB) OE: Inputs from different ORs are indicated by different colors; dispersed ensemble of neurons OB: Specific combination of glomeruli whose spatial arrangement is similar among individuals. Partially overlapping combinations of OR inputs generate distinct odor perceptions The olfactory bulb has a stereotyped map of OR inputs A). A single OR gene probe hybridized to sensory axons in 1 or 2 glomeruli on either side of the olfactory bulb B). Different OR probes hybridized to different glomeruli and those glomeruli had similar locations in six different bulbs.

Schematic diagrams showing the organization of odorant receptor inputs in the olfactory epithelium (OE), olfactory bulb (OB), and olfactory cortex (OC) Inputs from different ORs are segregated in different neurons and glomeruli in the OE and OB. In contrast, it appears that different receptor inputs overlap extensively in the OC (A) and that single cortical neurons receive signals from a combination of receptors (B)

The lock and key theory of odorant-receptor interaction does not address how diverse chemical structures have the same odor perception

Is the electronic swipe card model a better explanation than the lock and key?

The olfactory cortex has a stereotyped map of OR inputs Organization of inputs from the M5 (yellow) and M50 (pink) odorant receptors in the olfactory epithelium, bulb, and cortex. Black lines and abbreviations indicate different areas of the olfactory cortex. AON: anterior olfactory nucleus; PC: piriform cortex; OT: olfactory tubercle; Amg: olfactory nuclei of amygdala; EC: lateral entorhinal cortex.

The human taste system Cortical processing unclear All converge to NTS, then thalamus Nerves VII, IX, X from different regions of the mouth

The human taste system Human Olfactory System

Taste buds and taste papillae

receptor cells in bud; renew every 10 days or so 5-20 axons leave the bud; integration must be happening !! Salty, acidic, sweet, amino acid, bitter ALL represented by cells in the bud Salty, acidic, sweet, amino acid, bitter ALL represented by cells in the bud Bitter cells do not directly contact nerve – indirect through sweet and amino acid cells

Peripheral innervation of the tongue

Sensory transduction in taste cells

Molecular mechanisms of taste transduction via ion channels and G-protein-coupled receptors

Main points to remember Largest family of genes; ORs are GPCRs 1 OR expressed/neuron; can detect many odorants Even though many OR genes initially selected for expression, only one will dominate and remain expressed Odorant sensory neurons converge on a few glomeruli in the OB Partially overlapping combinations of OR inputs generate distinct odor perceptions in the olfactory cortex Taste system; salt and acids use ionic channels Other taste receptors use GPCRs The neural coding for taste system uses a labeled line code