Neurology 400 - Special Senses: Smell

-Genetic evidence suggests there are hundreds of ___________ ___________ -Ability to recognize ___________ different odours depends on patterns of activity in the brain that arise from activation of many different combinations of ___________ ___________ -In olfactory reception, a ___________ ___________ develops and triggers one or more nerve impulses

-Genetic evidence suggests there are hundreds of *primary scents* -Ability to recognize *10,000* different odours depends on patterns of activity in the brain that arise from activation of many different combinations of *olfactory receptors* -In olfactory reception, a *generator potential* develops and triggers one or more nerve impulses

In the case of the mitral to granule cell dendo-dendritic synapse, which NT do mitral cells release and which NT do granule cells release?

-Mitral cells release the excitatory NT *glutamate* -Granule cells release the inhibitory NT Gamma-aminobutyric acid (GABBA)

Special senses (5)

-Smell -Taste -Vision -Hearing -Equilibrium

What is the purpose of the Orbitofrontal Area of the Frontal Lobe?

-odour identification & discrimination -what exactly are we smelling?

What are the steps of Olfactory Transduction (7)

1. *Odorant binds to olfactory receptor protein* in plasma membrane of olfactory hair (cilia) 2. Olfactory receptor protein *couples to G-protein*, together they activate *Adenylate Cyclase* 3. Adenylate Cyclase produces *Cyclic AMP (cAMP)* 4.* cAMP opens Na+ channels* 5. *Na+ ions enter olfactory receptor* 6. *Depolarization* may generate AP 7. *AP propagates axon*

1. What NT do Mitral Cells release: 2. What NT do Granule Cells release:

1. Mitral = *EPSP* = *Glutamate* 2. Granule = *IPSP* = *GABA*

What 2 very different cell types do Basal Cells develop into?

1. Olfactory Receptors 2. Epithelium

What are the 3 types of cells in the olfactory epithelium?

1. Olfactory receptors 2. Supporting Cells 3. Basal Cells

Olfactory Pathway

1. Olfactory receptors => 2. Olfactory nerves => 3. Olfactory bulbs => 4. Olfactory tracts => 5. Cerebral cortex & Limbic System

Where do the Olfactory Tracts project to?

1. Primary Olfactory area of Cerebral Cortex aka: Olfactory Cortex 2. Limbic System/ Hypothalamus

Complete absence of smell sensation:

Anosmia

What makes up Right & Left Olfactory nerve?

Approx 20 (40 total) bundles of Olfactory receptor axons on each side (R & L)

How long do olfactory receptors live?

Approx 30 days b/f being replaced by new Basal cells under going cell division

What is the source of input and output for the olfactory bulb? What is the implication of this?

As a neural circuit, the olfactory bulb has one source of sensory input (axons from olfactory receptor neurons of the olfactory epithelium), and one output (mitral cell axons). As a result, it is assumed that it functions as a filter, as opposed to an associative circuit that has many inputs and many outputs.

What is the responsibility of the Primary Olfactory Area (Olfactory Cortex)?

Conscious awareness of smell (begins)

Distortion of smell sensation:

Dysosmia

What cranial nerve innervates Supporting Cells & Epithelium?

Facial (CN VII)

Which nerve innervates both epithelium and glands?

Facial (CN VII)

Why do we get watery eyes and a runny nose when we inhale substances such as pepper and ammonia?

Facial (CN VII) innervates both Olfactory (Bowman's) Mucus Glands and Lacrimal Glands in eyes

Basal dendrites of Mitral cells are connected to interneurons known as:

Granule Cells (IPSP)

In which part of an olfactory receptor does olfactory transduction occur?

In the olfactory hairs of an olfactory receptor

-Type of Dysosmia -Sensation of smell in absence of odorant:

Phantosmia

Glomeruli are also permeated by dendrites from 2nd order neurons which in turn output to the olfactory cortex --> what are these 2nd order neurons called?

They are called Mitral Cells (EPSP)

What cranial nerve detects *noxious stimuli* from *posterior nasal cavity*?

Trigeminal Nerve (CN V)

-located w/i nasal cavity -serve to direct inspired air toward olfactory epithelium in upper posterior region (2 names):

Turbinates aka: Nasal Conchae

-form of temporal lobe epilepsy -occurs before seizure onset -only occurs if seizure takes place in same part of brain responsible for smell -hallucinations of taste, smell and inappropriate chewing mvmts are prominent features:

Uncinate Fits

Where is the Primary Olfactory Area (Olfactory Cortex) located?

*-medial aspect of temporal lobe* -base of frontal lobe

The synapse between *mitral* & *granule* cells is of a rare class called...

*Dendro-Dendritic* (both sides of synapse are dendrites that release NT)

Molecule added to natural gas to give it an odor and warn of leaks:

*Ethyl* Mercaptan (Detected at 1/25 billionth of a milligram per ml of air)

What do Granule Cells produce?

*Lateral Inhibition* b/w Mitral Cells

Is threshold for odors high or low?

*Low* only very low concentraions of molecules of certain substances need be present in air -Adaptation to odours occurs quickly

Smell of rotten cabbage:

*Methyl* Mercaptan

Which hemisphere exhibits greater activity during olfactory processing?

*Right* Hemisphere

T/F; Olfactory sensations are the only sensations that reach cerebral cortex w/o 1st synapsing in thalamus?

*True* (but smell reaches Limbic System which Thalamus forms part of)

Are Olfactory receptor axons myelinated or unmyelinated?

*Un*myelinated

Olfactory receptor -_____________ neuron with an exposed _____________ -shaped _____________ and an _____________ -Axon projects through _____________ _____________ ending in _____________ _____________

-*Bipolar neuron* with an exposed *knob-shaped dendrite* and an *axon* -Axon projects through *cribriform plate* ending in *olfactory bulb*

Where does smell sensation project to after entering Primary Olfactory Area (Olfactory Cortex)?

-*Orbitofrontal* Area of Frontal Lobe

Why does smell project to Limbic System & Hypothalamus?

-*emotional* and *memory-evoked* responses to odours -e.g. sexual excitement upon smelling a perfume; nausea upon smelling a food that once made you violently ill; odour evoked memory of childhood experience

Describe the neural circuit of the Olfactory Bulb:

-1 source of sensory input (axons of olfactory receptor neurons) -1 output (mitral cell axons)

How many and where are the Olfactory foramina located?

-20 Olfactory Foramina on each side of nose, right & left (40 total) -Located in *Cribriform plate* of *Ethmoid bone*

Rate of olfactory adaptation

-Adaptation = decreasing sensitivity -Olfactory adaptation is rapid --> 50% in one second, complete in one minute.

Other ways to mess up smell

-Head trauma leading to fx of cribirofm plate may cause cerebrospinal fluid rhinorrea and potential meningitis -Paransal sinus endoscopy may lead to violation of cribiform plate and potential infectious complications -Olfactory structures also can be injured during craniotomies involving anterior cranial base...

Olfactory dysfunction is associated w/ what pathologies:

-Parkinson disease -Alzheimer disease -Huntington chorea -Obsessive-Compulsive Disorder

What other types of interneuron cells are located within the Olfactory bulb?

-Periglomerular Cells: synapse w/i & b/w glomeruli -Granule Cells: synapse w/ mitral cells

What is Lateral Inhibition?

-capacity of an excited neuron to reduce activity of its neighbors -disables spreading of AP from excited neurons to neighboring neurons in lateral direction.

Glomerular Layer

-layer of Olfactory Bulb -receives direct input from Olfactory Nerves -made up of axons from approximately ten million olfactory receptor neurons in olfactory mucosa:

Glomeruli -located within _______________ _______________ -ends of _______________ cluster in _______________ structures -each receives input primarily from _______________ _______________ neurons that express the same olfactory receptor.

-located within *Glomerular Layer* -ends of *axons* cluster in *spherical* structures -each receives input primarily from *olfactory receptor* neurons that express the same olfactory receptor.

Supporting Cells -What are they? -What do they provide? -What else do they do?

-mucous membrane cells lining nose -provide physical support, nourishment & electrical insulation of olfactory receptors -Also help detoxify chemicals coming into contact with the olfactory epithelium

Olfactory Bulbs

-paired masses of gray matter located *below frontal lobes of cerebrum* & *lateral to crista galli of ethmoid bone* -termination location for Olfactory Nerves

Olfactory Hairs

-part of olfactory receptor that responds to inhaled chemicals -made up of cilia that project from dendrite

Basal Cells -What type of cells are they and where are the located? -What are they continually undergoing and why?

-stem cells located b/w bases of supporting cells -continually undergo cell division to produce new olfactory receptors (which live for only a month or so before being replaced)

how many receptors for olfaction are contained w/i olfactory epithelium?

10-100 million

Are Olfactory receptors 1st or 2nd order neurons?

1st order

How many pathways does the Olfactory Tract form?

2

Which cranial nerve is the Olfactory nerve?

CN I

-Type of Dysosmia -Sensation of bad smell not related to a specific odor, or associated w/ olfactory stimuli usually considered to be pleasant:

Cacosmia

What is the result of the dendo-dendritic synapses' bi-directionality?

Can cause mitral cells to inhibit themselves (auto-inhibition) as well as neighbouring mitral cells (lateral inhibition)

What type of cell are *Supporting Cells*

Columnar Epithelial Cells

What cranial nerve innervates Olfactory (Bowman's) Glands?

Facial (CN VII)

Does adaptation to odors happen fast or slow?

Fast initially, then slow (By 50% in approx first second, complete insensitivity to certain strong odours about a min after exposure)

Olfactory receptors respond to chemical stimulation of an odorant molecule by producing a ____________ potential, thus initiating the olfactory ___________.

Generator Response

-Pathology of *reduced ability* to smell -affects half of those over age 65 and 75% of those over 80 -causes incl neurological changes (head injury, Alzheimer disease, Parkinson disease); certain drugs (antihistamines, analgesics), or steroids; and smoking

Hyposmia

What is the hypothesized functional role of lateral inhibition?

May be involved in boosting the signal-to-noise ratio of odour signals by silencing the basal firing rate of surrounding non-activated neurons.

chemicals that have an odor and can therefore stimulate olfactory hairs (cilia) are called:

Odorants

In which part of an olfactory receptor does olfactory transduction occur?

Olfactory Hair (Cilia)

-axon terminals of Olfactory Nerves form synapses w/ dendrite and cell bodies of Olfactory bulb neurons -extend posteriorly and form:

Olfactory Tract

What do olfactory receptor axon bundles travel through?

Olfactory foramina

Where do olfactory sensations NOT synapse, unlike other sensations?

Olfactory sensations are the only sensations that reach the cerebral cortex without first synapsing in the thalamus.

Olfactory Pathway details

On each side of the nose, about 40 bundles of slender, unmyelinated axons of olfactory receptors extend through about 20 olfactory foramina in the cribiform plate of the ethmoid bone. These 40 or so bundles of axons collectively form the right and left *olfactory (I) nerves*. The olfactory nerves terminate in the brain in paired masses of gray matter called *olfactory bulbs*, which are located below the frontal lobes of the cerebrum and lateral to the crista galli of the ethmoid bone. Within the olfactory bulbs, the axon terminals of olfactory receptors form synapses with the dendrites and cell bodies of olfactory bulb neurons in the olfactory pathway. Axons of the olfactory bulb neurons extend posteriorly and form the *olfactory tract*. Some of the axons project to the *primary olfactory area* of the cerebral cortex; located at the inferior and medial surface of the temporal lobe, the primary olfactory area is where conscious awareness of smell begins.

Where do other axons of the olfactory tract project?

Other axons of the olfactory tract project to the limbic system and hypothalamus and account for emotional and memory-evoked responses to odours (e.g. sexual excitement upon smelling perfume, nausea upon smelling food that once made you violently ill, odour-evoked memory of childhood experience)

-Type of Dysosmia -Sensation of smell in absence of appropriate stimulus:

Parosmia

What type of messenger is Cyclic AMP?

Second Messenger

What do olfactory bulbs do?

The olfactory bulbs transmit smell information from the nose to the brain, and are thus necessary for a proper sense of smell.

Term referring to conversion of chemical stimulus (smell) energy into graded potential in a sensory receptor:

Transduction

T/F; the CNS has some involvement in adaptation w/ smell?

True (details unknown)

Olfactory Glands -AKA? -What do they produce and why?

aka: Bowman's Glands Produce mucus which moistens surface and dissolves odorants so that transduction can occur.

why do certain odors and tastes evoke strong emotional responses or a flood of memories?

b/c impulses for smell and taste propagate to limbic system (and to higher cortical areas as well).

Why are olfaction & gustation considered chemical senses?

b/c of interaction of *molecules* w/ receptor cells

What is *Adenylate Cyclase*:

enzyme that converts ATP or ADP to Cyclic *AMP* (cAMP)

Olfactory Epithelium ◆ _____ square inch of membrane holding ___-______ million receptors ◆ Within a total area of ________ ◆ Covers ___________ ___________ ___________ and ___________ ___________ ◆ extends along ___________ ___________ ___________ ◆ _____ types of cells

◆ *1* square inch of membrane holding *10-100* million receptors ◆ Within a total area of *5 cm2* ◆ Covers *superior nasal cavity* and *cribriform plate* ◆ extends along *superior nasal concha* ◆ *3* types of cells