9/23 Chemical Senses - Matisse

Question 1

chemical senses in humans

Answer 1

1. olfaction/smell
2. gustation/taste
3. trigeminal/pain
4. pheromones?

Question 2

smell

Answer 2

olfaction : detection of volatile compounds (odorants) by olfactory epithelium of nose

• over 1k compounds can be detected, incl non-natural substances
• implication: olfaction is an open system capable of adapting and signaling info from an indeterminate environment

Question 3

anosmia

Answer 3

anosmia: olfactory dysfunction

• serious → puts a person at higher risk for toxic exposure
• can be associated with diseases/conditions

primary causes

• nasal/sinus diseases
• occlusion: deviated septum/tumors
• craniofacial trauma (olfactor nerve shearing)
• smoking
• toxic exposure
• genetic (specific anosmia - lower sensitivity to some odors - is common)

secondary causes

• endocrine: adrenal cortical insuff, DM, Kallman syndrome, Turner syndrome
• neurological: Alzheimer’s, Parkinson’s, Huntington’s chorea
  
  • poss bc actively dividing neurons more susceptible to these diseases
• cancer tx: chemo and rad treatments hit chemosensory stem cells hard

Question 4

anatomy of olfaction

importance of mucus

Answer 4

bundle of nerves comprising CN I

• made up of bundles of axons (10-100axons/bundle) of olfactory receptor neurons (ORNs) embedded in olfactory epithelium where they can receive signals from airborne odors (via olfactory cilia)
• ORNs continually replaced every 30-60 days from basal stem cell pop

mucus: important bc it immobilizes odorants to be detected via olfaction

Question 5

olfactory bulb organization

Answer 5

ORNs make excitatory glutaminergic synapses with OB cells in structures called glomeruli

• comprised of terminating axons of ORNs synapsing on mitral cells and tufted cells
• periglomerular cells serve as interneurons interconnecting cells within/across diff components of OB
• approx 5k present in humans → each one receiving inputs from ORNs expression ONE receptor type!

axons of thousands of ORNs expressing same OR converge at a SINGLE glomerulus, which represents the summed activity of all ORNs that express that single OR

• convergence increases sensitivity of olfactory system, enhances signal sent to brain for activity from that receptor

Question 6

central neural pathways mediating olfaction

Answer 6

anterior olfactory nucleus houses cell bodies of cells which synapse with mitral cells and also hit the contralateral olfactory bulb

• loss of AON, granule, periglomerular neurons might be responsible for impaired olfaction in Alzheimer’s!
  
  • all derive from anterior subventricular zone, are generated throughout life

medial stria connects two olfactory bulbs

lateral stria is main output tract → projections innervate cells in…

• medial temporal lobe (explains link of olfaction to memory!)
• orbitofrontal olfactory area

key: no thalamic relay!

Question 7

role of cilia in olfaction

process

desensitization

Answer 7

site of olfactory sensory transduction

• odorants at cilia → depolarizing/inward current
• odorants at cell bodies (embedded in olfactory epithelium) → no/weak depolarization

contain odorant receptors

• 7 transmembrane G-protein coupled receptors (large C terminal interacts with G-proteins)

in general…

• odorant binding to OR → increase in intracellular cAMP
• cAMP stimulates opening of cation channels → depolarization

desensitization: in OSNs, activated signal transduction mols are targeted for neg feedback reg

Question 8

mechanisms of odor desensitization/adaptation

Answer 8

majority of GPCRs display rapid loss of responsiveness in continuing/recurring presence of agonist or stimulus

• allows it to maintain ability to respond to other odors beyond the one that is present continuously

mechanisms:

1. receptor phosphorylation → uncoupling of receptor from Gproteins
2. internalization of cell surface receptors to cytosol
3. reduced receptor mRNA or protein synth → downreg of receptors (quantity)

Question 9

neural encoding of olfactory info

Answer 9

neurons can have diff sensitivity

1. broad sensitivity
2. specific sensitivity
3. narrow sensitivity

neurons also have diff thresholds for diff odorants

• perception of odor can change as a fx of its conc

odor recognition depends on which receptors activated & how strongly

• array of receptor activation → unique pattern of glomeruli activation that is consistent between individuals

Question 10

conductive vs sensorineural anosmia

Answer 10

conductive losses: loss secondary to obstruction of nasal airflow to olfactory cleft

• ex. chronic rhinosinusitis (CRS), allergic rhinitis, polyps, tumors

sensorineural losses: losses secondary to damage to/dysfx of olfactory nerves between path of olfactory receptors → olfactory bulb → processing centers in brain

• ex. loss of smell after upper resp inf, head trauma, toxins, congenital diorders, Alz disease, MS

Question 11

unilateral vs bilateral anosmia

Answer 11

unilateral: damage to olf epithelium, olf nerve, olf bulb, olf tract

bilateral: destruction of olf cortex, olf pathways posterior to trigone where tracts divide must be bilateral to affect olf function

• unilateral anosmia often compensated for by contralat nostric

Question 12

Kallmann Syndrome

etiology of the 2 sx!

tx

Answer 12

congenital, irrev form of hypogonadotropic hypogonadism associated with anosmia

• anosmia secondary to underdeveloped/absent olf bulbs or tracts
• delayed puberty due to lack of GnRH-releasing neurons in hypothal

heterogenous genetic disorder, males affected 5:1

sx often present at puberty

• delayed puberty is the main prob that presents

etiology: during development, olfactory placode is the source of two subset of cells that will separate during neuronal migration

1. ORN cells (migrate to olfactory epithelium)
2. GnRH releasing cells (migrate to hypothalamus

tx: hormone replacement tx for secondary sexual chars and fertility

• males: testosterone replacement
• females: gonadal steroid replacement, cyclic estrogen replacement

cannot rescue anosmia :(

Question 13

taste

Answer 13

gustation : direct contact of water-sol compounds with tongue pappilae

• higher threshold for perception than olfaction!!!
• i.e. olfaction is much more sensitive than taste (nano vs millimolar conc)

five primary taste modalities

1. sweet → sugar, aspartame
2. sour → protons
3. bitter → lg variety of chem
4. salty → Na, K
5. umami → free a.a.s (ex. MSG)

Question 14

anatomy of taste

Answer 14

taste cells clustered into taste buds on 3 morphologically distinct lingual papillae

1. fungiform (anterior 2/3) - 25%
   
   • CN VII (chorda tympani branch → geniculate ganglion)
2. circumvallate (posterior 1/3) - 50%
   
   • CN IX (lingual branch → petrosal/inf glossophar ganglion)
3. foliate (post edges - epiglottis, post pharynx) - 25%
   
   • CN X (sup laryngeal branch → inferior vagal ganglion)

all project into nucleus solitarius → VP medial nucleus of thalamus → gustatory cortex (insular region, frontal operculum)

• many of projections are bilateral

approx 4k taste buds in human oral cavity

taste buds are embedded in papillae

• open onto epithelial surface via taste pore
• taste cells continually replaced from basal stell cell pop (approx 2 week turnover)

Question 15

taste transduction in taste cells

Answer 15

taste cells are NON-NEURONAL, but are electrically excitable / can generate APs

• activity relayed by sensory neurons that innervate at basal pores
  
  • Na/K (salty) and H (sour) act directly on ion channels
  • bitter, sweet, umami tastants act via G-protein mediated intracellular 2nd-messenter cascades
• ultimately causes depol of sensory cell → release of serotonin to neurons that will transmit info to the brain

Question 16

ion channel-mediated taste transduction

Answer 16

salty: Na influx via Na channels
sour: H influx via Na channels or blockade of K channels (normally open at RMP)

sweet and umami and bitter: GPCRs

Question 17

taste perception

models for taste encoding

Answer 17

taste stimuli encodes quantitative and qualitative aspects

the specific complement of taste receptors that a person has can dictate aspects of what they perceive → influences dietary choices, health

models

1. “labeled line code” : taste info transmitted via specific receptors/cells that are “tuned” to particular qualities of the stimuli [DIRECT]

• activity in one neuron type is necessary and sufficient to represent a given sensory attribute
• distinct types of taste info are transmitted throughout taste system along specific pathways that preserve the fundamental taste quality
• evidence: diff tastes can light up diff parts of the gustatory system

2. “ensemble coding” : pattern of responses to a particular stimulus (varies across receptors/cells) is the essential quality → taste perception is a synthetic sense [INDIRECT]

• evidence: expts supporting a summed response to taste

Question 18

taste adaptation

Answer 18

taste receptors adapt to ongoing presence of stimulus, but mechs are not understood

• chemical left on tongue for long enough time → stops being perceived (ex. saliva)

to obtain full taste of foods, EITHER

• freq change types of foods being tasted
• wait sufficient time between helpings

Question 19

taste dysfx

Answer 19

true gustatory dysfx is rare → up to 80% of a meal’s flavor is result of olfactory input, so loss of smell often interpreted as loss of taste

• usually, chemosensory loss patients DO NOT los taste

causes

• oral health problems
• meds
• viral inf

Question 20

trigeminal chemoreception

Answer 20

function: detection of noxcious stimuli

• nociception via general somatic efferents
• occurs through stimulation of polymodal nociceptive fibers when chem irritants come in contact with face/oral cavity

exposure triggers variety of responses:

• incr salivation, tearing, sweating
• decr resp reate
• bronchoconstriction

→→→ dilute irritant stimulus, reduce intake

Question 21

anosmia

Answer 21

lower level sensitivity (lower threshold for detection of compound) is lost

• might still be able to detect the compound, just at a MUCH HIGHER LEVEL

Question 22

pheromones

what are they

what can they signal

organ in animals

Answer 22

gender-specific substances secreted by individs into environment (urine, glandular secretions), received by other individs of same species → cause specifix rxn

ex. definite behavior, devpt process

signals are involved in:

• gender identification
• reproductive status of potential mates
• social dominance status/aggression
• bonding of mother with young

in animals, need vomeronasal organ

Question 23

pheromones and humans

Answer 23

humans DO NOT have vomeronasal organ

• starts to develop during gestation, but disappears before birth

DO have many geners that are hologous to VMO receptor genes in other lower orgs, but most appear to be pseudogenes

some pheromone responses can be partly mediated by primary olfactory system in rodents…

other evidence that olfactory system could be primary site of odorant and pheromone processing in humans