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Developmental Neurobiology > Development of Touch and Nociception > Flashcards

Development of Touch and Nociception Flashcards

1
Q

what triggers a sense of touch generally

A

mechanoreceptors - they are depolarised by a mechanical force on the skin which generates an AP

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2
Q

what are the 4 types of mechanoreceptors?

A

merkel, meissner, ruffini, pacinian

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3
Q

what do merkel receptors detect?

A
  • pressure
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4
Q

what do meissner receptors detect?

A

flutter

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5
Q

what do ruffini receptors detect?

A

stretching

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6
Q

what do pacinian receptors detect?

A

vibration

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7
Q

are the receptors which detect touch the same as those that detect pain?

A

no- nociception

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8
Q

what stimulates nociceptors generally?

A

mechanical, heat, cold, chemical

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9
Q

do nociciceptors have specialized anatomically recognisable endings?

A

no- all the same generally when you look at them

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10
Q

what detemines the sensory neuron function of the nociceptors?

A

the specialized transduction channels

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11
Q

what channel is associated with touch reception?

A

MS (low threshold)

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12
Q

what channel is associated with painful reception?

A

TRPA1, TRPV1,2, MS (high threshold) and ASICS

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13
Q

where are all of the cell bodies of sensory neurons?

A

in the DRG

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14
Q

where do the sensory neurons synapse?

A

at the CNS in the dorsal horn of the spinal cord

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15
Q

describe an experiment which looks at the timing of sensory reflex arc development. what did they find?

A
  • take the pup fetus from the mother
  • at different stages in development
  • 21 days is when the pups are born
  • the scientists touched different parts of the body and asked if you could get a reflex movement from different parts of the body
  • they found that at 16 days there was very little response
  • at 17 days there seemed to be more response- more response in the upper part than in the lower.
  • not until the 20th day is the reflex arc formed to the same extent in the caudal region
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16
Q

where do mechanoreceptors and nociceptors arise from?

A
  • the neural crest
  • can see these cells migrates around E9
  • the NC migrate around E9 and then within 7 days they become an entire set of sensory neurons and innervate the skin etc
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17
Q

how is the size of the sensory neurons in the dorsal root ganglion related to their function?

A
  • the large cells (A cells) are the mechanoceptors: touch. They are also the proproceptors that are used for position sense
  • the small cells (C cells): nociceptors for pain and thermoreceptors for temperature
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18
Q

at E12 what has happened ?

A

the cell bodies of the sensoty neurons are in the DRG but they have differentiated in terms of size

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19
Q

what are the genes that are important for neuron specification?

A

there are certain geens which are expressed- neurogenin 1 is required for sensory neurons and neurogenin 2 is required for nociceptor development

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20
Q

what are the general (non geentic) waves of sensory neuron specification? what does this say about development?

A
  • at E9.5 it begins. The premigratory NC. the decision that these NCs will become sensory is made before the cells have reached the DRG: they are sensory neuron commited. This is true of the mechanoceptors but the nociceptors stay multipotent for longer and only become committed after migration at around 10.5-11.5 . this shows that the commitment of mechano is in advance of nociceptors. you may want the nocicceptors to come first because they will keep animals alive but you could also say that the ability of the young to bond with its mother which requires mechano is more important and maybe if you are attacked as a lion as a new born, what would be the point of having nocicpetors because you cant do anything about it.
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21
Q

when isn nrg-1 critical?

A

it is required for the commitment of the nociceptors durin the post migratory stage of nociceptor commitment

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22
Q

when is neurogenin 2 critical?

A

it is critical during the migratory stage of the sensory mechanoceptors in order to specify them as mechanoceptors

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23
Q

what are the runx genes?

A
  • they are important at arond E10.5- when the two groups of noci and mechan have divided and you want to make sub groups
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24
Q

what is the role of runx3?

A

it is involved in determinng whether the pre commited mech (no or low runx3) or prop cells (runx3)will become mechanoreceptors or sensory receptors (will they be in the tactile in the skin or proprio in the muscle spindles)

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25
Q

what i runx1 involved in?

A

determining which on the nociceptors will express peptidergic neurons (no runx1) or non peptidergic (runx1)

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26
Q

what is the role of pptidergic vs non peptidnergicneurons ?

A

??

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27
Q

which neurotrophins support nocicepors (peptinergic)?

A

NGF (trkA)

28
Q

which neurotrophins support mechanoreceptors?

A

BDNF (trkB)

29
Q

which neurotrophins support proprioceptors?

A

NT3 (trkC)

30
Q

where are the neurotropins attarcting the neurons coming from?

A

the target (skin target for example)

31
Q

for how long do the nerves in the limb need growth factor?

A

need it for as long as 10 days post birth

32
Q

what does runx3 expression mediate?

A

they allow the axons to release the receptors that they need to in order to survive- at high levels in induec trkC to be expressed and at low trkB

33
Q

what does runx1 expression mediate?

A

the nociceptors initially all express trka but then the expression of runx1 allows the non peptidergic neurons to downregulate trkA

34
Q

what is the geenral role of cell autonomous expression and external cues in sensory receptor development?

A
  • the expression of the different runx genes allows the cells to express different receptors which allows the neurons to respond to different signals from their target
35
Q

what happens when you change the expression pattern of neurotrophic factors from the skin in terms of neural development?

A
  • you mess up the normla development of the sensory neurons
36
Q

whta happens to the expression pattern if neurons that stop expressing trkA? (the non peptidergic neurons)

A

they start to express Ret (NT receptor) and they become responsive to GDNF. and these become pacinian corpsucles in the skin- when you remove ret by KO you get no specielaised pasinian corpuscles

37
Q

what happens when you KO ret?

A
  • you get no pacinian corpuscles
38
Q

which receptors reach the skin of the feet first?

A
  • the mechanoreceptors
39
Q

is it possible to record inidicual mechanoreceptors AP when they arrive at the embryo skin?

A

yes

40
Q

what are the properties of the immature mechanoreceptor?

A
  • there are defined small receptive fields, different physiological receptor types, poor frequency coding (not good at givig higher freq at an increased intensity) and few spikes- the basics are there
41
Q

what are the properites of immature nociceptors?

A
  • polymodal nociceptors (will respond to mechanical but also to heat and to chemical etc)
  • frequency coding is fairly good
  • they can become sensitised by inflammatory meidatiators (firing easily at lower thresholds)
42
Q

what expeiment shows that you can affect the development of mechanoreceptors?

A

if you increase the expression of NT3 you can ncrease the sensitivity of mechanoreceptors

43
Q

where do nociceptors terminate?

A
  • superficial laminae I and II
44
Q

where do mechanoreceptors terminate?

A

deeper laminae III- V (compared to the nocicepotrs)

45
Q

how do the termination regins of the mechanoceptors and the nocicceptors change over time>

A
  • in the adult the nocicpeotrs terminate in the superfical laminae I and II and the mechanoceptors in the depper laminae
  • but in the neontaal animal: the mechanoceptors teminate in the superficial laminae too- they overlap
46
Q

how can you view the changes of postnatal refinemine of Abeta afferent fibre termination fields along the length of the cord, what is found?

A
  • you measure the the activity of the neurons along the body and in the paw and you see tat initially they are very large areas of activity but then they decrease over time and the regions of activity become smaller.
47
Q

what is the difference between the sensation from nociceptors and mechanoreceptors during development and adulthood?

A

A fibre synaptic activation of dorsal horn cells is strong at birth; C fibre activation not clear until the second postnatal week-around day 10

48
Q

what is the development of mechanoreceptor and nociceptor sensory neurons dependent completely on?

A

sensory input

49
Q

what experiment demonstrated that the central processing of the neonatal touch and anociception is less precise than in adults?

A
  • if you shine a laser on one side of the animal it is not good at moving its tail away from the area of stimulation but by the third week of life it can do this perfectly- there is a critical region between postnatal day 12-20
50
Q

describe an experiment which demonstrated that touch input is required for the development of accurate nociception?

A
  • if you keep the tail of a neonatal pup in local anasthetic then the pups ability to develop the nociceptive reflex which normally occurs between E 18-20 is delayed until the numbing is removed- isnt an innate response
51
Q

if rearing an animal with its tail numbed is seen as applying negative sensory stimulus, explain an expeirment which looked over stimulating the animal between p13 and p20? what did this show

A

animals were raised on a shaking platform- constant sensory movment that is not normal and suggested this muffles specific sensations- when thye are brought up in a shaking platform, the A fibres will not eventually move back to the deep layer of laimina. This shows that the type os sensory inpu that goes on during animal development is every important

52
Q

what happens to the receptive field of cutaneous receptors during development, how is this demonstrated?

A
  • you can record the stimulation rate of DRG neurons when exposed to stimuli on the paw of the rat
  • you find that a greater portion of the paw is represented by each DRG neuron in the young animal than in older animals.
  • the DRGs recieve input frm a much larger area
  • as the animal grows up, the receptive field decreases
53
Q

describe the third experiment which emphasies the need for sensory input into the DRG during development

A
  • block the sensory input by blocking NMDA rceeptors- do not allow normal y sensory input into the ventral hoorn
  • if you do this then the receptive field of the DRG does not shrink in size ove rdevelopment.
  • this shows how much we need sensory input for the development of the nervous system
54
Q

how can you investigate how central touch and pain processing in the somatosensory cortex devleops in humans?

A
  • reording EEG activity (activity that arises from the brain but you record from the brai surface)
  • you find that the developing cortex in response to sensory stimulation starts out in early development by producing lots of random bursts
  • then as the animal develops you cross over from non specific bursting acivity to specific acivity by tactile and nociceptive
  • this may be the point at which infants can distinguish between touch and noxious stimulation
55
Q

how did they stay the change in cutaneous receptive field in the long vs older mouse paw?

A

they stimulated the paw and looked at the activuty in the dorsal horn and looked at which areas on the paw stimulated a specific region of the neurons in the dorsal horn-it decreased in some over time

56
Q

how did they find out what was involved in the postnatal reduction of receptive field size in mice postnatally?

A
  • they did the experiment where the receptive field of a mouse paw that is reprinted by a specific region of the DRG- they found that when they implemented a chronic blockade to the of NMDAR then they got a reduction in the ability to fine tune the receptive field
57
Q

what is the difference in timing of the peptinerpic and the non peptinerpic neurons?

A
  • the non peptingergic which are IB4+ enter the dorsal horn after the peptiergic ones
58
Q

how does the outgrowth from the DRG proceed?

A
  • in two waves- the fibres first and the C fibres afterwards
59
Q

when do the A fibres reach the epidermis?

A

around day E15-17

60
Q

when do the C fibres reach the skin?

A

around E18-20

61
Q

what is the difference between the stimulus response sensitivity acquirement in the A fibres and the C fibres?

A

the A fibres do not need time to acquire it but the C fibres require a longer postnatal period to acquire it

62
Q

when do the first afferent fibres enter the dorsal horn? when do the C fibres enter it?

A

at E13 - at E18-19- from the outset these C fibres terminate in a somatotopically precise manner

63
Q

when do the A fibres withdraw from the lamina I and II?

A

the first 3 postnatal weeks

64
Q

how does the spinal cord develop?

A

in a ventral to dorsa lmanner- lamina I and II last

65
Q

how does the responsiveness to nociceptor stimulus in the dorsal horn to nociceptor stimulation change during development? how was this shown?

A

C fibre evoked activity in dorsal horn cells develops gradually over the post natal period, a lover percentage of dorsal horn neurones with nociceptive inputs are observed in the first weeks of lifee compared with adults and elliptical stimulation of C fibres fails to evoke synchronised burst spikesin dorsal horn neurons or motor neurons. C fibres irritant mustard oil induces only a weak flexion reflex and c-fos levels in the dorsal horn postnatally
- when you add Capsaicin- there is a glutamate release in the superficial horn for P0 and a significant increase between P0 and P5 so there is some C fibre response not a lot

Developmental Neurobiology (10 decks)

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