Touch and Hearing (mechanosensation) Flashcards
what are the different variations of touch?
touch is not well understood but can differentiate between gentle and more severe touch
what do mechanosensory neurons generate in response to touch?
- rapid ionic currents
- in Abeta fibres
- sugests neuronal activation is likely to be direct gating of an ion channel
what channels have been assocaited with touch?
- TREK, TRPS, Degenerin/Emac, Piezo
how were the channels associated with touch identified?
- via mutant screens in model organisms give general principals of mechanisms
how is touch organised in C.elegans?
- PVD covers the body
- sensroy neurons for different touch
- current is passed by C.elegans PVD sensory neurons in response to touch
what are PVDs?
- are touch sensitive
- found within the hypedermic
how do PVDs function?
deflection upon pressure causing movement of the branched structure
what is the proposed opening of channels in the branch points in C.elegans?
- as the touch is applied
- deflects the dendrites
- action potentials are generated
what occurs as a result of detection due to deflfection in C.elegans?
amplification
detection
transmission
what touch do C.elegans respond to?
- harsh touch, reversal in the usual sinusoidal movement
how were C.elegans screened for touch mutants?
- mutants generated by mutagenesis
- antimals negatively reponding to touch will be kept, bred and re-tested
- used geneting mapping and recombination with strain in mutants against a related
- mapping of the mutant phenotype
- mutants were characterised, cloned and identified
what did they identify in C.elegans for touch sensitivity?
a MEC complex
what is the structure of the MEC complex?
- 3 components
- in the ECM: large domain stiff proteins, roped, globular structures
- 3 channels: MEC4, MEC6 MEC40, a complex - ion channels
- inside the cell: MEC7,MEC12, components of microtubules
what is the mechanism for touch sensitivity in C.elegans?
- mechanism where a channel is anchored to the cytoskeleton and the ECM
- pressure causes movement between the two structures and physically opens the channel
what is the strutcure of the channel involved in touch sensitvity in C.elegans?
- cystein rich domains in the extracellular loop act as a gate on the channel so normally blocked
- extracellular loop binds to the matrix and cytoskeleton and moves the cystiene rich domain out of the way
what is the result of mutations at residue A713?
- causes death of neurons
- first idendified at MEC4
- alanine to valine substituion at 713
- alanine (small aa)
- valine (bulky), acts to keep the channel constituviely open
- sensory dies by excitotoxicity
- degenerins
how do hairs affect touch?
they are the tranducers of touch
what is the function of hairs?
- act as a levers
- sit in a socket
- can be attached to a neuron via the neuronal dendritic cap
- deflection of the hair by touch moves the dendritic cap to activate a current in the neuron
- can be direct or indirect
how are mouse whiskers tranducers of touch?
mouse whisker follicle hair is associated with merkel cells
- upon deflection of the hair deflects merkel cells and activates associated sensory afferent neurons
- merkel cells are acting as mechanosensors
what is the molecular mechanosensory in mice?
Piezo
what happens in mice genetic KO of the Piezo2 channel?
- diminishes sensroy afferent response to hair defelction in whisker follicle cells
what is the function of Piezo2 in mice?
- rapidly inactivateing piezo2 channels confers mechanosensitivity to Merkel cells
- Piezo2 is in the slowly adapting type 1 neurons which are also mechanosensitive
- Merkel cells release NTs from dense core vesicles to slowly adapting type 1 aferents
what are Piezo channels?
can generate current in mechanically deflected membrane
how have experiments proved the function of piezo channels?
- when piezo proteins are expressed in non-mechanosensitive cells current is generated by positive or negative pressure
- cells not expressing piezo proteins do not generate in response to positive/negative pressure
- respond to a deflection of the membrane
what happens if you KO piezo channels in drosophila?
- drosophila only have 1 type of piezo channel
- KOs of piezo are less sensitive to harsh touch than wild types
- larvae would normally roll away from harsh touch but the knockouts dont respond
what are Piezo channels specific for?
harsh touch
what are the main principles of hearing?
vibrations of an object cause the surrounding air to condense and rarify waves travelling at 700mph
what soundwaves can humans detect?
30Hz to 20,000 Hz and amplify volume 100 fold
what do differences in the physical dimensions of sound result in?
differences in perceptual dimension
what are the factors of sound?
- amplitude (loudness)
- frequency (pitch)
- complexity (timbre)
- also get direction from having 2 ears
why does the ear differentiate sounds?
to detect individual component frequencies of complex sounds
how does the ear direct sound?
- channels sound towards detection mechanism
- towards the tympanic membrane
- sound vibrates the tympanic membrane
- moves the auditory ossicles
- ossicles transmit the vibration to the inner ear (particularly the cochlea)
how does sound travel in the cochlea?
- makes ossicles move vibrating the oval window (in the membrane which attaches to the scala vestibuli)
- moves the sound into liquid
- vibration in the fluid then travels around the cochlea
why does the cochlea move the sound into liquid?
- fluid is incompressible
- sound moves much more quickly
what does th oval window allow?
- vibration
- outlet for compression
- if you didnt have an outlet of pressure your cochlea would burst
where does the vibration travel to?
enters the cochlea travels through the scala vestibuli and is detected in the organ of corti
how is sound detected in the cochlea?
- as vibration moves it becomes a travelling wave
- point of maximum displacement of the wave describes a loaction in the cochlea
- each frequency generates a peak at different positions along the choclea
- achieved through hair cells
what are the hair cells in the cochlea?
- inner and outer hair cells between the tectorial and basilar membranes
- vibrations of the cochlea causes a shearing force
- the hairs are displace
what is kinocilium?
made of microtubules
what is sterocilium?
made of actin filaments
what do kinocillium and sterocillium respond to?
- respond to shear stress induced by vibration moving the tectorial and basilar membranes
why are ankle and tip links important?
- ankle links anchor at the base
- tip links: anchor and cause the opening of channel
what are tip links?
molecular link between stero cilium and kinocilium
what is the structure of tip links?
- made of cadherin proteins
what is the role of tip links?
- vibration moves and tips the sterocilia toward the kinocilium
- stretches the tip link and opens
what are CDH23 and PCDH15?
- link to a channel complex
- long proteins linked to the cytokseleton
- dont know the composition of the channel
what do mutations of CDH23 and PCDH15 linked to?
- ushers syndrom
- familial deafness
what does stretching of the tip links allow?
- movement of K+ and lymph into the cell
- causes a depolarisation
- influx of Ca2+
- release of neurotransmitter onto an afferent neuron
how do insects hear?
- in the antenna
- movement/vibration of the 3rd antennal segment rotates the segment within the antennal segment 2
what is involved in stretching structures called scolopales?
- complex makeup
- neurons with dendrites stretched inside them
- in the cilium there are 3 TRP channels
what are the 3 TRP channels in hearing in insects?
nanchung, inactive and nompc
what is the role of TRP channels in the hearing of insects?
- contribute to signal amplification and feedback control in insects
- mechanosenstitve hearing cells produce vibrations in the absence of sound
what is the role of nanchung and inactive?
- dampening of vibration amplification, controlling feedback
what is the role of Nomp C?
contribute to production of vibration promoting feedback
