Lecture 2

Olfaction and Taste

General Information

  • Taste transduction occurs on the tongue and the roof of the mouth via taste receptor cells.

  • Taste receptor cells must interact with taste and communicate information to the brain.

  • Taste buds are located in the infoldings of membrane invaginations (papillae).

  • Grooves on the tongue trap taste, allowing it to be sensed by taste buds.

  • Taste buds have a taste pore where taste interacts with taste receptor proteins on taste cells.

  • Each taste bud comprises approximately 50 cells of several types that encode taste.

  • Unlike the olfactory system with labeled lines, the taste system is less understood in terms of wiring and coding.

Taste Cell Types

  • Type One Cells:

    • Electron dense in the cytoplasm.

    • Primary purpose is to secrete mucus to provide an aqueous environment for taste binding to receptor proteins.

    • May also be responsible for sensing salt.

  • Type Two Cells:

    • Lighter cytoplasm in EM.

    • Terminate with microvilli (foldings of the primary cilium) to increase surface area for taste receptor proteins within membranes.

    • Mediate GPCR-mediated senses.

  • Type Three Cells:

    • Similar to type two cells but with only a single microvillus.

    • Accumulate serotonin.

    • Make traditional synapses with cranial nerves, serving as the primary afferent synapses.

    • Interact with type two cells via paracrine activity (ATP release).

  • Type Four Cells (Basal Cells):

    • Located at the bottom of the taste bud.

    • Can differentiate into any of the other taste cell types, allowing for regeneration after damage (e.g., burning the tongue).

Regeneration

  • The taste system, like the olfactory system, can regenerate because taste receptors are exposed to the external environment.

Taste Bud Composition

  • Each taste bud contains about 50 cells with different functions.

  • Electron micrographs of taste receptor cells stained with serotonin (5-HT) show staining of a central cell that makes conventional synapses with cranial nerves.

  • Type three cells constitute 5-15% of cells in the taste bud and form classic chemical synapses on nerve fibers.

  • Output from the taste bud goes through the type three taste cell, even if encoded in type two cells, indicating paracrine signaling within the bud.

Action Potentials and Neurotransmitters

  • Taste cells generate sodium action potentials to release neurotransmitters onto nerve terminals.

  • The primary neurotransmitter is believed to be glutamate.

  • Cranial nerves receive input from taste receptors depending on their location (front, back of the tongue, roof of the mouth).

  • The seventh cranial nerve is particularly important.

Taste Modalities

  • Taste is divided into five modalities:

    • Bitter

    • Sweet

    • Umami (sensed by monosodium glutamate).

    • Sour (related to the number of protons).

    • Salty (gated by changes in extracellular salts).

  • Bitter, sweet, and umami are GPCR-mediated, while sour and salty are ionotropic receptor-mediated.

Nerve Activity and Taste Modalities

  • Nerve activity recordings from a cat tongue in the 1930s showed sensitivity to multiple taste modalities within a single axon of the cranial nerve.

  • Nerve fibers convey modality information by modulating firing rate.

  • Loose patch recordings from taste buds indicate individual cells have sensitivities for different modalities.

  • Nerve fibers coming out of the tongue that sample from type three cells have all modalities mixed, while individual cells within the taste bud show labeled responses to particular modalities.

Molecular Biology and Taste Transduction

  • Identifying genes expressed in taste receptor cells helps understand taste bud composition.

  • The cranial nerve output is mixed across modalities.

  • The whole bud responds to all modalities.

  • Individual cells within the buds respond selectively to individual modalities.

GPCR Mediated Taste Modalities

  • Bitter: T2Rs (class two receptors), 25-35 genes with small N terminals, bind lipophilic bitter compounds within the membrane.

  • Sweet: Dimer of taste receptor family one receptor two (T1R2) and taste receptor family one receptor three (T1R3), large N terminal, binds water-soluble sugars.

  • Umami: T1R1 dimerized with T1R3, senses amino acids (e.g., glutamate), not metabotropic glutamate receptors.

  • The T1R3 is shared between sweet and umami receptors.

  • In situ hybridization shows receptor expression in different cells within the bud without colocalization.

Experiments by Charles Zucker

  • Specific receptor knockouts affect action potential coming out of the seventh cranial nerve (chorda tympani).

  • Knocking out T1R1 or T1R3 removes umami.

  • Control mice show sensitivity to monosodium glutamate, monopotassium glutamate, serine, and alanine.

  • T1R1 or T1R3 knockouts eliminate this activity.

  • T1R2 knockouts are unaffected.

Bitter Taste Receptors

  • One cell can express multiple T2Rs.

  • Knocking out a single receptor can selectively affect one bitter taste, leaving others unaltered.

  • Multiple T2Rs in a receptor cell can mitigate this.

  • Obliterating phospholipase C beta eliminates all transduction.

  • Re-expressing phospholipase C in the control of the promoter of any one of the bitter genes restores all bitter sensation.

Individual Differences in Taste

  • Taste varies among individuals due to differences in the number and complement of taste receptors.

  • The proportion of bitter receptors can vary, leading to different levels of action potential firing.

G Protein and Effector Molecule

  • G protein: Gustducin (related to transducin and G alpha o).

  • Effector molecule: TRP channel.

  • Knocking out phospholipase C beta or TRPM5 eliminates transduction in all GPCR-mediated modalities.

  • The receptors expressed determine the difference between sweet, bitter, and umami taste cells.

Ionotropic Taste Receptors

  • Sour: Mediated by polycystic kidney disease-like ion channels (PKDL1 or 2).

  • Salty: Mediated by different channels at different concentrations; low sodium uses epithelial sodium channels blocked by amiloride, while high sodium uses another mechanism.

Sour Taste Receptors

  • Made of two receptor types (PKD2L1 and PKDL3).

  • PKD2L1 is expressed in every type of cell within the whole mouth.

  • PKDL3 is expressed on the major taste receptors but maybe not on the roof of the mouth.

  • Ion channels are located close to the taste port.

  • Ablating cells that express PKD2L1 eliminates sour but leaves other modalities fine.

  • Also mediates the change sensation of carbonation.

  • Carbon dioxide goes through a rapid conversion to bicarbonate using carbohydrates.

Salty Taste Receptors

  • Directly gate ion channels.

  • Increasing extracellular sodium concentration opens channels and depolarizes the cell.This process plays a critical role in taste perception, as saltiness is primarily detected through these receptors.

  • Changes in current reflect changes in membrane resistance.

  • Patch recordings show that resistance depends on whether sodium is present.

  • Epithelial sodium channels are blocked by amiloride.

  • Two components of salt response as you go from 10mM external sodium to 500mM external sodium:

    • ENaC channel: Partially blocked by amiloride at low sodium concentrations.

    • Other Channel: Insensitive to amiloride, more prominent at high sodium concentrations.

Summary of Taste Receptors

  • Sweet: T1R2 and T1R3 dimer

  • Umami: T1R1 and T1R3 dimer

  • Salty: ENaC channels mediate low concentrations. Another unidentified receptor at high concentrations

  • Sour: Polycystic kidney disease channels (PKD)

Taste Processing Pathway

  • Different cranial nerves go to the Geniculate Ganglion.

  • Goal of every sensory process is to condition action potentials to feed the input into the computational things

  • The cortex is a mess with little discrimination.

Major Problems and Questions

  • Type two cells are metabotropic (GPCR-mediated).

  • Type three cells are largely sour.

  • What are the salt receptors on Type one cells?

  • Only type three cells make synapses onto the cranial nerve.

  • How does integration within the taste bud of, like, all these different cell types integrate the activity into the output of the type three glutamate groups?

  • Organizational issues and discrimination in taste are limited compared to other senses due to the smaller number of receptors.