Lecture 2: Touch Detection

Question 1

What is somatosensation?

Answer 1

comprises multiple sensory processes

• temperature
• pain
• itch
• proprioception
• touch (tactile sensation)

Question 2

What is the tactile sensation pathway from the periphery to the CNS?

Answer 2

touch reaches the CNS via dorsal root afferent neurons

Question 3

Where are the cell bodies of primary afferent neurons located?

Answer 3

• dorsal root ganglia (body)
• cranial ganglia (head)

Question 4

What are the two branches of primary afferent neurons?

Answer 4

• peripheral axon branch – to the skin
• central axon branch – to the spinal cord and brainstem

Question 5

What special feature does the peripheral axon branch of a primary afferent neuron have?

Answer 5

specialized mechanosensory endings in the skin

Question 6

What can electrophysiological recordings from sensory afferents tell us?

Answer 6

can reveal coding properties

Question 7

What are slowly adapting fibres?

Answer 7

rate of APs (rate code) is higher at the beginning of the stimulus, then activity is maintained throughout the remaining length of the stimulus

Question 8

What are rapidly adapting fibres?

Answer 8

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

Question 9

Do all touch receptor types produce the same afferent response?

Answer 9

no – different touch receptor types produce different afferent responses

Question 10

What are raster plots?

Answer 10

plots that show action potentials over time, and allow us to examine the trial-by-trial variability of activities/responses of different neuron types

Question 11

What cell type gives the most precise representation of a stimulus in a raster plot?

Answer 11

merkel cell – very close to the skin surface, and therefore good at tactile sensation (ie. braille)

Question 12

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?

Answer 12

• 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

Question 13

Sensory Receptor Types – Table

Answer 13

• slowly vs. rapidly adapting
• type of stimulus it detects
• fibre type

Question 14

How are the cellular and molecular substrates of touch experimentally determined? How is it a problem to determine these?

Answer 14

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

Question 15

Why has it been so difficult to identify mammalian mechanosensory channels?

Answer 15

• 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

Question 16

What is RNAi?

Answer 16

process that leads to destruction of mRNA that matches the sequence of the added double-stranded RNA

Question 17

What does RNAi allow researchers to do?

Answer 17

allows them to knock down the expression of a specific gene without having to make a mutation in the DNA encoding the gene

Question 18

How was Piezo discovered?

Answer 18

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

Question 19

What do Piezo family genes encode?

Answer 19

channel subunits with many transmembrane domains

Question 20

What does Piezo2 mediate?

Answer 20

merkel cell light touch – Piezo2 is expressed in merkel cells

Question 21

What is Piezo2 necessary for?

Answer 21

• mechanosensitive currents in merkel cells
• normal behaviour responses to light touch

Question 22

What was the Piezo2 mutant?

Answer 22

a ‘conditional knockout’ where Piezo2 is only mutant in merkel cells – full knockout mouse would die

Question 23

What is a sufficiency experiment that could be conducted to see if Piezo2 is sufficient for normal behaviour responses to light touch?

Answer 23

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

Question 24

What molecules can mechanical force be sensed by (force-transducing molecules)?

Answer 24

• ENaC family
• TREK1
• TRP family
• Piezo family

Question 25

What is the common element of force-transducing molecules?

Answer 25

mechanically-gated ion channels – can turn force into energy very quickly

Question 26

What are the 3 things that (usually molecular/genetic) papers always want to accomplish?

Answer 26

• 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

Question 27

How do we show that Factor X (neuron, gene, protein, RNA, etc.) is NECESSARY for a particular phenomenon or activity?

Answer 27

remove something that is normally there and show that there is some effect on the phenotype (lose what that factor is doing)

Question 28

How do we show that Factor X (neuron, gene, protein, RNA, etc.) is SUFFICIENT for a particular phenomenon or activity?

Answer 28

add something that isn’t normally there and show that it confers that particular response

Question 29

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?

Answer 29

expression or activity or something that makes sense with the system

Question 30

What receptor types is touch detected by?

Answer 30

detected by a variety of receptor types, which each respond to a particular type of touch