Lecture 2: Touch Detection Flashcards
What is somatosensation?
comprises multiple sensory processes
- temperature
- pain
- itch
- proprioception
- touch (tactile sensation)
What is the tactile sensation pathway from the periphery to the CNS?
touch reaches the CNS via dorsal root afferent neurons
Where are the cell bodies of primary afferent neurons located?
- dorsal root ganglia (body)
- cranial ganglia (head)
What are the two branches of primary afferent neurons?
- peripheral axon branch – to the skin
- central axon branch – to the spinal cord and brainstem
What special feature does the peripheral axon branch of a primary afferent neuron have?
specialized mechanosensory endings in the skin
What can electrophysiological recordings from sensory afferents tell us?
can reveal coding properties
What are slowly adapting fibres?
rate of APs (rate code) is higher at the beginning of the stimulus, then activity is maintained throughout the remaining length of the stimulus
What are rapidly adapting fibres?
burst of activity when a force is applied, followed by a quiet period while the stimulus is being held, followed by a small burst of activity when the force is removed
Do all touch receptor types produce the same afferent response?
no – different touch receptor types produce different afferent responses
What are raster plots?
plots that show action potentials over time, and allow us to examine the trial-by-trial variability of activities/responses of different neuron types
What cell type gives the most precise representation of a stimulus in a raster plot?
merkel cell – very close to the skin surface, and therefore good at tactile sensation (ie. braille)
What possibilities are there for how touch afferent neurons encode different somatosensory stimuli so that a poke feels different than an itch, which feels different from a pinch?
- multiple receptors with different levels of sensitivity – low vs. high threshold receptors
- receptive field of different neurons – slowly vs. rapidly adapting, receptors that respond specifically to vibrations/touch/etc.
- different touch sensations rely on different receptor types
Sensory Receptor Types – Table
- slowly vs. rapidly adapting
- type of stimulus it detects
- fibre type
How are the cellular and molecular substrates of touch experimentally determined? How is it a problem to determine these?
every patch of skin has multiple (4-5) different types of mechanosensitive sensory neurons – these terminate with elaborate anatomical and physiological specializations, but their afferent axons are intermingled
Why has it been so difficult to identify mammalian mechanosensory channels?
- problem 1: different touch receptor types likely depend on different channels
- problem 2: touch is sometimes detected by multicellular complexes that involve interactions between cells and with extracellular matrix (ie. Merkel cells) – this is very difficult to reconstitute in vitro
- problem 3: different animals utilize different mechanosensitive channels for touch, making screening in model organisms less effective
What is RNAi?
process that leads to destruction of mRNA that matches the sequence of the added double-stranded RNA
What does RNAi allow researchers to do?
allows them to knock down the expression of a specific gene without having to make a mutation in the DNA encoding the gene
How was Piezo discovered?
using RNAi screening in cell culture
- researchers knew that N2A (non-receptor) cells had mechanically-gated currents in vitro
- researchers transfected RNAi ‘knockdown’ constructs against ~70 candidate transmembrane proteins into N2A cells, finding one (Piezo) that reduce mechanosensory currents
What do Piezo family genes encode?
channel subunits with many transmembrane domains
What does Piezo2 mediate?
merkel cell light touch – Piezo2 is expressed in merkel cells
What is Piezo2 necessary for?
- mechanosensitive currents in merkel cells
- normal behaviour responses to light touch
What was the Piezo2 mutant?
a ‘conditional knockout’ where Piezo2 is only mutant in merkel cells – full knockout mouse would die
What is a sufficiency experiment that could be conducted to see if Piezo2 is sufficient for normal behaviour responses to light touch?
add Piezo2 to a cell that normally does not show light touch responses and illustrate that it actually confers light touch sensation to those cells
What molecules can mechanical force be sensed by (force-transducing molecules)?
- ENaC family
- TREK1
- TRP family
- Piezo family
What is the common element of force-transducing molecules?
mechanically-gated ion channels – can turn force into energy very quickly
What are the 3 things that (usually molecular/genetic) papers always want to accomplish?
- to show that Factor X (neuron, gene, protein, RNA, etc.) is necessary for a particular phenomenon or activity
- to show that Factor X is sufficient to generate that activity
- to show that Factor X is present at the right time, in the right place, to naturally confer that activity
How do we show that Factor X (neuron, gene, protein, RNA, etc.) is NECESSARY for a particular phenomenon or activity?
remove something that is normally there and show that there is some effect on the phenotype (lose what that factor is doing)
How do we show that Factor X (neuron, gene, protein, RNA, etc.) is SUFFICIENT for a particular phenomenon or activity?
add something that isn’t normally there and show that it confers that particular response
How do we show that Factor X (neuron, gene, protein, RNA, etc.) is present at the RIGHT TIME, in the RIGHT PLACE for a particular phenomenon or activity?
expression or activity or something that makes sense with the system
What receptor types is touch detected by?
detected by a variety of receptor types, which each respond to a particular type of touch
