Taste and Olfaction

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Taste and Olfaction
Taste is primarily involved in feeding- used to
identify nutritious or toxic
substances allows both detection of high
concentrations of nutrients and low conc. of
toxins-- 100s of mM to mM mammals perceive
only 5 tastes- salty, sour, sweet, bitter, umami
a significant factor in taste is smell- used to
discriminate many tastes
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Sensing Taste
taste cells develop from epithelial cells and
uses microvilli and linked receptors/ion
channels 50-100 cells clustered together in
taste buds on tongue, palate, epiglottis 3
classes- fungiform, foliate, and circumvallate
linked to separate nerves all project to the
brainstem, a very old region of the brain
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Sensing Taste
taste cells survive only 10 days and must connect
to nerves to survive cutting nerve kills taste
neurons taste cells do not change their
characteristics when innervated by different
nerves- connections required for a trophic
factor not development connections must form
repeatedly throughout life
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Sensing Taste
2 7-pass transmembrane families detect sugars,
amino acids, bitter taste link to G
proteins salty and sour link directly to ion
channels and evolved independently T1R has 3
genes that detects sugars and amino acids using 3
criteria found in right place loss of
receptor loss of taste add receptor lets
cells respond T1R2T1R3 activity
sugars T1R1T1R3 activity amino acids all have
low affinity binding to several compounds, and
mutations can limit the range of chemicals
detected
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Sensing Taste
T1R3 is a coreceptor with T1R1 and T1R2, but all
3 bind substances T2R family senses bitter
taste phenylthiocarbamide (PTC) is mediated by
T2R38, and there are 2 main polymorphisms
found on chromosome 7 T2R has a small
extracellular domain while T1R has a large
one 25 human genes in family, linked in arrays
suggesting rapid expansion of the
family different receptors activated by
different bitter compounds generally at lower
concentrations-- more specific receptors
usually detect lower concentrations
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Sensing Taste
7-pass transmembrane proteins link G proteins
intracellularly gustducin Ga subunit found
in some but not all sweet/bitter neurons
presumably other Ga subunits can also work
here gustducin binds to phospholipase C PLC-b2
to produce IP3 and DAG TRPM5 ion channel is
also required for taste mechanism going from
PLC-b2 is proposed, but not proven
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Sensing Taste
sour and salty tastes are sensed by ion channels,
primarily H 2 different TRP (transient receptor
potential) channels seem required for sour
detection salt detection is harder to localize-
seems to be a general epithelial sodium
channel no receptor-- just diffuses in
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Sensing Taste
different taste receptors are found on different
cells and detectors do not overlap-- cells
detect either sweet or umami, not both best
evidence suggests tastes are not easily mapped to
parts of tongue synthetic tastes can be
genetically engineered into particular
neurons and change animals preferences depend
ing upon the promoter (which determines the
type of cell), T1R drives preference, T2R
avoidance mice like sugar water avoid bitter
tasting (contaminated) water
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Sensing Taste
3 nerves innervating the tongue project
topographically to the solitary tract nucleus
of the medulla in the brainstem anterior tongue
connects to rostral nucleus posterior to
caudal medulla projects through several
intermediates to thalmus, then cortex topographic
connections are maintained also project to
forbrain regions conrolling feeding, autonomic
regulation links also to motor regions
controlling face/mouth muscles
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Sensing Taste
taste perception has 3 characteristics
intensity, quality and hedonistic mediated by
which neurons are activated and how
strongly intensity is thought controlled by
frequency of firing and the number of
responding neurons quality is mediated by
either segregated labeled lines or by
ensemble activity of all neurons CNS
recordings suggest ensemble hedonistic quality
ie. how much a person likes a taste is
controlled by external influences such as
experience or physiologic state
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Olfaction
can be amazingly sensitive and distinct-- humans
smell very poorly bloodhounds detect scents
days old-- incredibly sensitive even we can
discriminate approximately 10,000 odors 1000
receptors (all G protein coupled) detect
different ligands odors tend to be small and
volatile olfactory neurons are bipolar, with
apical dendrites having 6-12 cilia coated in
mucus for trapping smells axon projects to the
olfactory bulb
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Olfaction
odorant receptors are G-protein coupled receptors
similar to opsin varies most in TM3-5 where
other 7-pass receptors bind ligands receptors
are found in linked arrays of genes on several
chromosomes receptors may be very specific or
class specific most ligands are not known-
only 20 or so pairs have been identified each
olfactory neuron makes only 1 olfactory
receptor only 1 allele is expressed makes an
easy code for the brain- each neuron is odor
specific
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Olfaction
all Ga subunits of odorant receptors (Gaolf)link
to adenylate cyclase cAMP then activates a
cyclic nucelotide gated channel, depolarizing
the neuron letting in cations (primarily Na and
K, but also Ca2) Ca2 opens a depolarizing Cl-
current (ie. chloride is high in these
neurons, so it leaves the cell, raising the
membrane potential) channel activation is
converted into a frequency code more ligand
binding, more action potentials without Gaolf,
mouse pups die within days, unable to
nurse electrophysiology showed very little
odor response in mutants
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Olfaction
adaptation in olfactory neurons uses calcium and
occurs in stages high intracellular calcium
decreases open channel probability stage 2
reduces cAMP by calcium dependent silencing of
adenylate cyclase aka 'short term
adaptation' long term adaptation requires
guanylate cyclase and further kinases
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Olfaction
olfactory epithelia has 4 zones, with particular
receptors in each zone project to the glomeruli
of the olfactory bulb, anterior to cortex each
olfactory neuron projects to one glomerulus, with
each glomerulus expressing the same odorant
receptor as the olfactory neuron each smell
activates particular glomeruli patterns can
overlap, but are distinct the pattern for an
odor is fairly consistent for equivalent
stimulation conditions similar molecules
generally activate an overlapping subset of
glomeruli
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Olfaction
connectivity between olfactory neurons and
glomeruli seems to be partially controlled by
the olfactory receptor itself olfactory receptor
is found on the axon as well as
dendrite deletions of olfactory receptor
removes glomerular specificity misexpression of
a new olfactory receptor creates a new
target coupling to G protein intracellularly
is essential for guidance seems to be Gas
instead of Gaolf
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Olfaction
mitral/tufted cells in olfactory bulb form
synapses onto the glomerulus inhibitory
GABAergic periglomerular cells surround the
glomerulus and also have synapses onto the
mitral/tufted cells also form inhibitory
synapses on neigboring glomeruli-- adds
contrast granule cells below mitral/tufted cells
synapse with several glomeruli adding a second
layer of processing/contrast mitral/tufted cells
project to olfactory cortex, synapsing on
pyramidal cells same general cortical circuits
appear elsewhere in the cortex
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Olfaction
olfactory neurons must be renewed throughout
life-- constantly getting new
neurons ventricular epithelium of basal
forebrain migrate anteriorly, the anterior
migratory stream mechanisms are pretty much
unknown
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Pheromones- the Accessory Olfactory System
pheromones are species and gender specific
chemicals secreted by an individual that
confers information regarding social/reproductive
status pheromones cause stereotyped behaviors
consistent between individuals volmeronasal
organ has all of the pheromone receptors-
separate region of the nasal/oral cavity
related to taste receptors projects separately
to the accessory olfactory bulb, then to other
areas 2 layers of VNO neurons express
different receptors, with one receptor type
per cell but connect to multiple glomeruli in
overlapping patterns