Notesale: Turn your study into money

Document Preview

Extracts from the notes are below, to see the PDF you'll receive please use the links above

---

Taste and Smell: Chemosensation
Neuroscience Lecture 10- Sean Sweeney
Outcomes
Appreciate that taste and smell are chemosensory
Mammals: Taste is mediated by Taste Receptors (TR) (which are GPCRs) and ion channels
organised in the taste bud
...
- The picture is not quite clear! We don’t know how the
taste receptors come together to generate saliency (getting a dominant taste off a food)
...
Flys sense their chemical environment with much more than just their mouth eg
antennae
...
Plants
can also be chemosensitive, can move towards sources or food or nutrients and can move

away from things they aren’t too happy with
...
Be aware that this isn’t neuronal based!
Smell and taste guide food choice- have a nutritive value which can be positive and
negative
...
Flys also detect pheromones and we probably do as well but we
don’t know about it
...
But theres tests
where they put it on chairs and women are more likely to sit on those chairs
...
Also to mark territory by marking with olfactory
...
Also bitter/smelling things such as
poison which is typically bitter
...
Gustation requires direct contact
...

Sharks use olfaction- at a distance by being able to detect 1 billionth of a ml of blood many
miles away
...
So
there’s 900 can be detected in humans, these are different genes tuned to different
odorants
...
One category is umami which only came into western
vocabulary 15-20 years ago
...
We did not know about this till someone cloned the receptor
...
They add to the sensation of when we
eat
...

INFO ON POWERPOINT
Note that in insects and mammals, the major gustatory and olfactory organs are closely
associated: this may be evolutionary but also functional, odour is used to attract but still
assess before material is placed near the gustatory system
...

Taste receptors are also present in the gut, in enteroendocrine cells
...
Explains why eating glucose
produces more insulin production than direct injection into the bloodstream
...

Taste receptors for ‘sour’ in gut also reduce stomach emptying
...

Taste receptors also expressed in brain, and increase in T1R1 and T1R2 expression in
hypothalamus (involved in metabolic regulation) after 24h of food deprivation
...


Organised by other, more ancient processes
...

Salty is probably being transduced by ion channels ( usually Na)
...
Organic acids
Bitter- This is often a poison or something we normally avoid
...
Sean needs espresso to give him a kick up the bum
in the morning
...

Sweet- lots of energy
There are taste receptors T1R 2/3 cloned by someone which are the receptors for sweet
...
All of these are GPCRs
...
Prepare body for effective utilisation of the food
...
The ‘filliform’ papillae detect texture and fat may
be partially a texture within food
...

However, on first exposure, we often reject some tastants such as coffee, tho’ on
subsequent exposures ‘learn’ to like it
...

The receptors prime gut for digestion and preparing insulin
...
They are quite small, are invaginations except for in the funigorm
at the front of the tongue
...
Each of these buds/valley
shaped things have a pore at the top
...
This solubilizes the chemicals, making them available
...
But there’s also this
idea that back in 1905 people did experiments involving a taste map- putting salt on one side
of your tongue etc
...
All tastants can be tasted
all over your tongue
...
This is a taste bud which does
some of the sifting out of the saliency
NOTES FROM POWERPOINT
Tongue
Taste receptor cells are constantly renewed throughout life
...
Generates an interesting problem where the new taste receptor cells generate
new neuronal connections
...
The
GPCRS but can see the T1Rs have a larger extracellular domain
...
There’s only 3
T1Rs in the human genome so it’s not like there’s a huge diversity
...
It’s also low affinity and this
means it’s very difficult to saturate, so when you come across something sugar tasting, you
eat a lot, we are happy to continue eating something sweet
...


But there’s almost 30 T2Rs- bitter
...
These receptors have a much higher affinity
...
That’s more of a protective response, whereas sweet/umami is
appetitive
...
But can see the T1R3 is a
common channel, T2R are the GPCRS
...

So what we’ve done is recorded from a single afferent fibre, these are fibres going through
turning back up to the higher cerebal cortex
...

If you knock out T1R1, can see umami gone but all others intact
...
Knock out T1R3, the common subunit and see missing umami/sweet
...
The PKD
knock out is defective in tasting sour
...
Why? Because phospholipase C acts on the signaling cascade downstream of
GPCRs
...
It’s a
particular phospholipase C which is responsive to GPCRs
...

TRPm5 is TRP channel which can act as a store operated calcium channel, downstream of
the GPCRs to also knock out umami/sweet/bitter
...

NOTES FROM POWERPOINT
Many more genes for T2Rs in mammalian genome
The G-coupled taste receptors appear to evolve rapidly, v
...
Reflects differences in diet and
ecological niche
...
T1Rs are a major difference in taste preference
between mammals
...
T2Rs
have higher affinity, necessary to detect noxious foodstuffs more rapidly and at lower
concentrations to generate a safety margin
...


PKD2L1 is a TRP channel
...
clear evidence of a labeled line
...
In the experiment
they’ve taken the bitter receptor, which has a promoter, so it is only going to be expressed in
certain cells
...
They’ve also
taken a different promoter for one of the sweet GPCRs, a sweet promoter
...
The bitter receptor is now being expressed in the cells which normally
express the sweet receptor
...
This depends of the
concentration of the bitterness in the food
...

It’s a bitter compound, but its stimulating activity in a sweet responding cell
...
This is more of a labelled line- it will
activate the sweet cell by whichever means, stimulate one neuron and that’s the type of
response you get
...

The experiment is: a promoter (the 5’ regulatory region) for a ‘sweet’ receptor, is coupled to
a ‘bitter’ receptor, so that the bitter receptor is now expressed in (normally) ‘sweet’
responding cells
...
Mice now perceive the
‘bitter’ compound as ‘sweet’
...
BUT they don’t look like neurons
...
We characterise them as this as they have neuronal characteristics, but they're not
quite sensory neurons
...

These are directly contacted with the apical surface
...
As you get older your taste starts to fail
...

NOTES FROM POWERPOINT
Cell types and synapses in the taste bud
...
Asterisks mark Type
II (receptor) cells
...
Comp
...
(Royer and Kinnamon,
1991)
...
Presynaptic cells are immunostained (red) for aromatic amino acid decarboxylase (a
neurotransmitter-synthesizing enzyme that is a marker for these cells), and are distinct from
receptor cells, identified by GFP (green)
...
Neurosci
...
These cytoplasmic
extensions wrap around other cells in the taste bud
...
Bar, 10 µm
...
S
...
Chaudhari
...
The nucleus (Nu) of the presynaptic cell is at the top, and
neurotransmitter vesicles cluster near the synapse(s)
...
mt, microtubule
...
C
...


This cell is making direct contact with cell apical fibres
...
How these cells contact/communicate with the apical surface is unknown
...

1 a type 1 glial like cell, tends to wrap around other cell types more
...
Has no clear
contact with the sensory afferent fibres
...
The function
and mechanism by which this cell talks to others is unknown
...
However how they're gated is unclear
...
It looks like a sort
of gap junction; which releases ATP
...
P2Y on this type 3 cell also
...

3 presynaptic cell
...
There's the
activation of ?5’hydroxytrypdamine?- get secretion here of ?subordinin? which acts to
silence this neuron
...

That that forms what is sent down the pathway fibre to drive saliency
...
This classification incorporates ultrastructural
features, patterns of gene expression, and the functions of each of Types I, II (receptor), and
III (presynaptic) taste cells
...
They
also may clear extracellular K+ that accumulates after action potentials (shown as bursts) in
receptor (yellow) and presynaptic (green) cells
...
Salty taste may be transduced by some Type I cells, but this
remains uncertain
...
The extracellular
ATP excites ATP receptors (P2X, P2Y) on sensory nerve fibers and on taste cells
...
Sour stimuli
(and carbonation, not depicted) directly activate presynaptic cells
...
Tables below the cells list some of
the proteins that are expressed in a cell type–selective manner
...
i
...
the taste bud is an integrated taste organ allowing
tasting of mixed appetitive and aversive tastes to allow for saliency
...


Cellular
Taste GPCR activates the PLC and diacylglycerol 3 activates calcium stores
...

In the other type of cell- type 3 we have a sour tasting that often causes acidification
...


In the type 1 cell we’ve got salt which acts down a sodium channel
...

The TRPN5 is the depolarisation of 5HT
...

Still unclear
...

NOTES FROM POWERPOINT
Mechanisms by which five taste qualities are transduced in taste cells
...
The combined action of elevated Ca2+ and membrane depolarization
opens the large pores of gap junction hemichannels, likely composed of Panx1, resulting in
ATP release
...
T2R taste
GPCRs (bitter) do not have extensive extracellular domains and it is not known whether
T2Rs form multimers
...
Intracellular H+ is believed to block a proton-sensitive K channel (as yet
unidentified) and depolarize the membrane
...
(C) The salty
taste of Na+ is detected by direct permeation of Na+ ions through membrane ion channels,
including ENaC, to depolarize the membrane
...


Labelled line experiment- their cross fibre may not be acting outside the taste bud but acting
within it to generate some sort of code that may be in the 5’ pattern of the cation potentials

...


Summary
Dedicated taste receptors transduce nutritive quality to taste cells
Taste receptors expressed in 3-4 types of taste cell in taste bud
Mechanism by which taste is conveyed from taste buds to neurons unclear (no synapse,
complexity of ‘taste’ in a foodstuff)
Taste can have complex interactions with higher order sensory systems (somatosensory) to
generate flavour (temp/texture etc)
The mammalian olfactory system:
Closely linked with the respiratory and gustatory apparatus
Aided by turbulent air eddies (but still water soluble molecules binding receptors)

Olfaction: chemosensation at a distance!
Olfactory is chemosensitive at a distance
...
This
causes turbulence in the olfactory cavity
...


In epithelia, the sensory dendrites (much more like sensory neurons /neurons in general)
...

They're spread across this area where the olfactory cilia sense projections
...
Often these sensory neurons
have to reset up the wiring
...
The cell are also growing
all the time
...
There's some
pluripotency involved in these neurons
...
Therefore axonal growth and synaptogenesis are constantly occurring in the
vomeronasal tract
...
, (2004) Mice cloned from Olfactory Sensory Neurons
...
Small is very tightly
coupled to memory, don’t know why- probably evolutionary
...
There's only one receptor for each
olfactory sensory neuron which generates a topographic map or makes a line, olfactory
sensor A makes contact with identifiable glomerulus- a second order structure with another
neurons sending down its dendrites to meet the synapses that meet to induce the olfactory
...

NOTES FROM POWERPOINT
Anatomy of the rodent peripheral olfactory system
...
Axons of the OSNs in the main olfactory
epithelium comprise the olfactory nerve and innervate the olfactory bulb
...
(B) Each OSN of the main olfactory epithelium
expresses only one odorant receptor gene (OR A, OR B, OR C, etc
...
Neurons expressing a given OR are organized into broad zones along the
dorsal–ventral axis of the olfactory epithelium (OE) and converge to a common glomerulus
at corresponding dorsal–ventral zones in the olfactory bulb (OB)
...


GPCRs- have olfactory receptor, get G protein coupled reception and uses this G alpha,
activating the olfactory specific adenyl cyclase 3 to generate cyclic AMP which gates the
channel, generating an AP
...
Something
happens is that (don’t know how) in every mammal have 2 copies of gene, one is always
shut off and one is activated
...

NOTES FROM POWERPOINT
Signal transduction in the OSN
...
Binding of an odorant to its
cognate OR results in the activation of heterotrimeric G protein (Gαolf plus Gβγ)
...
cAMP gates or opens the cyclic nucleotide-gated (CNG) ion
channel, leading to the influx of Na+ and Ca2+, depolarizing the cell
...
In
addition, cAMP activates protein kinase A (PKA), which can regulate other intracellular
events, including transcription of cAMP-regulated genes
...
Selection of a particular
OR gene by the cell is thought to occur via interaction of a cis-regulatory locus control region
with the proximal promoter of a single OR gene within a cluster of OR genes
...
The mechanism underlying OR-mediated, OR gene silencing is at present not
understood
...


It’s not like the olfactory receptors are really type specific
...
It’s the pattern of activation that
represents molecular identity of the odorant
...
Graphic representation of the olfactory
receptor combinatorial code
...
Reflecting functional studies on individual odorant receptors, some
receptors are more narrowly tuned than others, and individual odorants can activate different
subsets (and numbers) of receptors
...
Discrimination and
appropriate responses therefore occurs at higher order structures such as the piriform cortex

In interest of time, this is more about the axon guidance! Don’t learn
...
The projection of OSNs in the olfactory
epithelium (OE) to their target glomeruli in the olfactory bulb (OB) can be considered along
the bulb's three principal axes
...

(B) Innervation of the lateral olfactory bulb is dependent on IGF signaling, which may
function to counteract a default tendency of all olfactory neurons to project medially
...
By modulating the expression levels of axon guidance receptors such as Nrp1, the
sensory axons are either more or less sensitive to guidance cues found in the OB or along
the projection pathway
...

The insect olfactory system is 2 to 3 orders of magnitude more sensitive than the
mammalian system
...
Have chemosensors on
other parts of the body apart from their nose
...
When a fly walks on a surface, it senses with their feet
...
Also
have a soft structure called the maxillary palp which also has sensilla
...
He’s got what all these
abbreviations mean in the note section of the slide (below)
...
These
sensory neurons the axon here, go back the way to the suboesophageal ganglion (SOG) to
the ‘Antennal Lobe’ (AL)
...
Same at this point again with insects as it is for
mammals smell is tightly coupled to memory
...
He identified the receptor and can see its in
a subset of neurons in the maxillary palp
...
On walking on a substrate with appetitive content, a
‘Proboscis Extension Reflex’ is generated, so flies detect food as they walk on it generating
an extension of the mouthparts to the substrate
...
Antenna and maxillary palp have sensory

‘projections’ known as sensilla, classified into Large and Small Basiconic and Coeloconic
...
Sensilla: 419 in male, ~457 in female – so
females may have a different set of odorants to work to
...
The antennal lobe sends projections to the
mushroom body, specifically to a structure known as the mushroom body calyx (MBC), a
large tripartite structure that is known to mediate olfactory memory
...


This is to make a point, don’t learn, learn principles!
In every type of olfactory receptor have OR83B because it’s an obligate sensory
heterodimer
...

They all have to couple to this in order to be functional
...

Sean Sweeney makes a shit joke about flies smelling
...
Smell can generate
flies to go together mating and aggression
...
See red box
...

There's a specific one which detects co2
...
However for a mosquito its positive- looking for
blood, follow co2! Same receptor can generate two different behaviours
Therefore we know receptors must pair to it

School of glomerusulus- packets of post synaptic dendrites
...
Can see they make particular junctions,
very hard, its not plastic
...
These neurons are positive for a
transcription factor called fruitless
...
2 X
chromosomes which turn on the TFs to make females
...
There's about 16 fruitless neurones in males which are positive, generating most
of the sexual behaviour of males
...

NOTES FROM POWERPOINT
11, cis-vaccenyl-acetate is exuded by male flies and causes aggregation behaviour
...
The glomerulus that OR67b
projects onto, expresses the transcription factor Fruitless, critical for generating divergent
sexual behaviour between males and females
...
So a single pheromone can elicit different behaviours in the two sexes
...

Conclusions:
Insects and vertebrates employ remarkably similar strategies for sensory transduction
and coding suggesting ancient origins for sensory systems
Sensory transduction is mediated by ‘molecular sensors’ which detect specific
sensory stimuli and transduce this signal to a generate a neuronal code

---