Taste

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Taste
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circumvallate papilla
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labelled lines

• There are five recognised modalities sweet,
  sour, bitter, salt umami.
• All mature taste bud cells have prominent
  microvilli.
• Taste bud cells are continuously renewed from a
  local population of stem cells and their
  half-life is about ten days.
• Type I "dark" cells are glial (supporting) cells,
  but also contribute to salty (chloride) tastes.
  The full salt flavour may also require sodium
  channels.
• Sub-populations of type II cells respond to
  sweet, bitter, umami (glutamate) and possibly
  fats. They release ATP which stimulates
  purinergic receptors on type III cells and also
  on sensory neurons.
• Type III cells signal "sour" after intracellular
  acidification. Only type III cells make synaptic
  connections, where they release serotonin.
• The sensory nerves are labelled lines but it is
  not known how they specifically communicate with
  the appropriate sensory cells.

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Taste bud
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Recognised tastes receptors

• Sour PKD1L3 or PKD2L1 (disputed)
• Salty ENaC or TRPV1 (disputed)
• Bitter T2R family about 30 members
• Sweet T1R2/T1R3 heterodimer
• Umami T1R1/T1R3 heterodimer plus
  other glutamate receptors?
• Fats?
• In addition to the taste buds, there is a
  closely-related family of entero-endocrine cells
  throughout the GI tract, which use similar
  transduction mechanisms to control food intake,
  digestion and incretin release.

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Bitter, sweet umami taste transduction
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gustatory adaptation

• It is difficult to study sensory adaptation to
  continuing taste stimulation and there are very
  few published reports.
• It has recently become apparent that taste
  sensitivity is modulated by external factors, and
  this has become a prolific area for research.
• Leptin, a cytokine produced by adipocytes (which
  reduces food intake and increases energy
  expenditure) inhibits the taste bud response to
  saccharin.
• Glucagon (which is produced in response to
  hypoglycaemia) increases the taste bud response
  to sucrose, while the incretin hormone GLP-1
  maintains and enhances the response to sweet
  stimuli.
• Ghrelin increases the response to salty and sour
  tastants, and oxytocin also seems likely to
  modulate these responses.
• Taste buds also respond to GABA, and it seems
  likely that complex networks of signalling
  molecules will be found to underpin taste bud
  physiology, just as they underpin other areas of
  the GI tract.

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Smell
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olfactory signal transduction 1

• Vertebrate odorant receptors (ORs) all belong to
  the immunoglobulin superfamily.
• Some mammals may have two thousand OR genes.
• Species (e.g. humans) with a poor sense of smell,
  have fewer OR genes, and many of these are
  inactive pseudogenes.
• Each OR can bind a range of molecules, but each
  gene has a unique pattern of binding affinities.
• Human olfactory receptor neurons (ORNs) live for
  about two weeks and are replenished from a local
  population of stem cells.
• Each ORN expresses one specific OR on about 20
  non-motile cilia.
• Olfactory cilia cannot be properly described as
  primary cilia because there is more than one per
  cell, but they are similar.
• All the ORNs expressing a particular OR converge
  onto one or two matching olfactory glomeruli
  within the olfactory bulb.

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olfactory signal transduction 2

• ORs are G protein-coupled-receptors (GPCRs) which
  activate adenyl cyclase type-III via the G
  protein, Golf
• cAMP opens a nonselective, cyclic-nucleotide-gated
  (CNG) cation channel, depolarising the ciliary
  membrane.
• ORNs express a Na/K/Cl cotransporter (NKCC10)
  which maintains a high intracellular chloride
• Ca2 influx through the CNG channels opens
  Ca2-activated chloride channels on the ciliary
  membrane
• Cl- leaves the ORN down its concentration
  gradient, which further depolarizes the cell and
  provides amplification.
• Internal Ca2 binds to calmodulin which initiates
  multiple negative-feedback pathways that
  facilitate adaptation.
• Action-potential generation in ORNs involves
  voltage-gated sodium channels and low
  voltage-activated (T-type) calcium channels.

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olfactory signal transduction 3

• Mammalian smell has great sensitivity and a very
  wide adaptation range, as might be expected for
  outward facing receptors.
• Adaptation in mammals occurs by a variety of
  mechanisms with very different time scales, and
  their relative importance is disputed.
• Olfactory adaptation in mammals may involve local
  negative feedback loops with calcium calmodulin
  (see previous diagram).
• Increased calcium export from ORNs may allow
  mammals to cope with sustained stimulation by
  high odorant concentrations.
• Increased phosphodiesterase activity may help to
  remove excessive concentrations of cyclic AMP.
• In addition, mammalian olfactory receptors may be
  phosphorylated, and / or internalised, and / or
  uncoupled from their G-proteins as part of the
  adaptation system.
• Expression of mammalian OR genes may be
  downregulated as part of a long-term adaptation
  mechanism.

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olfactory signal transduction 4

• Odorants produce a graded concentration-dependent
  depolarisation within mammalian olfactory cilia
  an analogue response.
• Spikes are superimposed on the receptor potential
  within the cell body of the ORN analogue to
  digital conversion.
• The axons from the ORNs to the corresponding
  glomerulus carry fully digital action potentials.
• The glomeruli are arranged in a fixed, inherited,
  spatial map, but related odours are not
  associated within the olfactory bulb.
• Olfactory processing involves contrast
  enhancement between different odours, similar in
  some respects to retinal processing.
• Calculation of time derivatives d(smell)/dt and
  d2(smell)/dt2 is probably important for following
  odorant trails.
• Sniffing and head movements provide mammals with
  additional information about the source of the
  smell.

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Olfactory and retinal processing
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Accessory olfactory areas

• In addition to the main olfactory area, many
  species have various accessory areas, such as the
  vomeronasal organ, which are specialised for the
  reception of social and sexual smells.
• Their function seems to be linked to the MHC
  system, with the result that many mammals prefer
  sexual partners that will optimise the immune
  capabilities of their offspring. It is disputed
  whether a similar system operates in humans.
• MHC proteins and a subset of ORs are also
  expressed in sperm, where they may participate in
  sperm chemotaxis, thereby ensuring that eggs are
  more likely to be fertilised by an
  immunologically compatible sperm.

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more slides to be added here

• There is one recent paper and three important
  recently published reviews, all of which are
  highly recommended. I am preparing slides from
  these, but this is taking me longer than
  intended. In any event, you ought to read them
• Kaupp (2010) Olfactory signalling in vertebrates
  and insects differences and commonalities.
  Nature Reviews Neuroscience 11, 188-200.
• Sibbering Benton (2010) Ionotropic and
  metabotropic mechanisms in chemoreception
  chance or design? EMBO reports 11, 173-179
• Kato Touhara (2009) Mammalian olfactory
  receptors pharmacology, G protein coupling and
  desensitization. Cell. Mol. Life Sci. 66,
  3743-3753
• Pluznick et al (2009) Functional expression of
  the olfactory signaling system in the kidney.
  PNAS 106, 2059-2064.

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Sibbering Benton (2010) Ionotropic and
metabotropic mechanisms in chemoreception
chance or design? EMBO reports 11, 173-179
Mammals have metabotropic ligand binding
receptors with second messenger signalling
cascades, which indirectly activate ion channels,
whereas insects use ionotropic receptors which
are directly gated by the chemical stimuli.
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Kaupp (2010) Olfactory signalling in vertebrates
and insects differences and commonalities.
Nature Reviews Neuroscience 11, 188-200.

• Key for next slide
• The vertebrate nasal cavity contains several
  olfactory subsystems the main olfactory
  epithelium (MOE), the vomeronasal organ (VNO),
  the Grüneberg ganglion (GG), the septal organ
  (SO) and guanylate cyclase D-containing cells
  (GCDs) in the MOE. Sensory cells of the MOE and
  the SO project axons to glomeruli of the main
  olfactory bulb (MOB). Sensory cells of the GG and
  GCDs in the MOE send their axons to the necklace
  glomeruli (NG). Sensory cells of the VNO send
  their axons into the accessory olfactory bulb
  (AOB). Olfactory receptor neurons (ORNs) in the
  MOE (right) have one dendrite, which ends in a
  dendritic knob. From each dendritic knob,
  approximately 15 cilia extend into the nasal
  mucus. ORNs are surrounded by supporting cells
  and are constantly generated from basal cells.

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Kaupp (2010) Nature Reviews Neuroscience 11,
188-200.
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from Kaupp (2010) Nature Reviews Neuroscience 11,
188-200.
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mammalian transduction
mammalian adaptation
Kaupp (2010) fig 3
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Figure 4 from Kraup (2010)Competing models of
insect OR signalling.Model a is considered
more likely.