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Neuroscience > Lecture 11 - Hearing, touch, movement and balance > Flashcards

Lecture 11 - Hearing, touch, movement and balance Flashcards

1
Q

What are some of the main features of mechanosensation?

A
  • can determine between strong and soft stimulus
  • 1 of the 5 basic senses
  • mechanosensory neurons generate very rapid ionic currents in response to touch
  • likely via direct gating initiated by hairs on the skin
  • TREK, TRP, Degenerin/Enac and Piezo are the channels involved
  • can adapt to touch
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2
Q

What are the neurons assocaited with touch and how were these established

A

Type II, non ciliated
-Multidendritic neurons (nociceptor neurons, muscle stretch receptos, visceral stretch receptor)
Type I, cilliated
-Bristles (macrochaetes, microchaetes, contact chemoreceptors, hair plates)
-Campaniform sensilla (haltere, wing)
-Chordotonal organs (Johnstons organ, fermoral ch organ)

Established via touching flies, worms and looking at response

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3
Q

What are the features of touch in c.elegans?

A
  • can distinguish between soft, hard, nose and sexual touch
  • stretch receptors just below the surface (in hypodermis)
  • dendrites cover the body surface
  • Neurons involved: e.g. PLM (body touch neuron),PVM, PVD, ALM, AVM
  • force is convered directly through contact with the body wall, through the deflection causing movement of a 2 branched structure (in menorah cells), causing the opening of channels
  • must be sufficent todepolarise touch sensitive neurons
  • only lateral movement across these linear structure will generate a potential in a dendrite
  • current carried by MEC-4 transduction-channel complexes
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4
Q

What are the features of touch in Drosophila?

A

-‘bristle morphology’ = sense touch/movement through dedicated groups of cells arranged to detect mechanical force through movement of a hair cell or stretch receptors
-bristle movement deforms the dendritic sheet of 2 mechanosensory neurons, leading to neuronal excitiation
-

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5
Q

What are the features of the development of mechanical sensation detecting organs in drosophila

A

-arise from simple developmental program including assymetyric cell division
1-neuroblasts [pI/SOP] (which have stem cell characteristics) divide, and one of the daughter cells recieves a set of proteins
2-a gradient of extracellular protein (notch - secreted) defines the cellular characterisation
3-other daughter cell lacks proteins
-cells known as either PIIb or PIIa
-a combination of intrinsic and extrinsic signals give rise to different types if sensory organs that are mechanosensitive:
-either hair cell (omat, chordatonal stretch receptor or mechanosensitive multidendritic cells)

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6
Q

Why are cillia critical in the struture of the extrasensory bristle and chordotonal organ? [drosophila]

A

-tubular bundle connects to the cillium

in chordotonal organ they must be connnected apically and basally to tightly packed microtubules

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7
Q

What are NomPA and where are they found? [drosophila]

A

NOMPA
-dendritic cap protein
-large extracellular domains which extend outside the cell and attach to the ECM
NOMPC
-TRPN protein
-29 ankyrin repeats enabling it to bind to other proteins (and therefore anchored in the membrane)

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8
Q

What type of TRP channel is only in the chordotonal organ and not the extrasensory bristle? [drosophila]

A

TRPV channels

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9
Q

What about the structure of the extrasensory bristle and chordotonal organ suggests they are used in hearing? [drosophila]

A

long, stiff filament shape

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10
Q

What is the Johnson’s organ and what is it for?

A
  • at the front of a fly’s head
  • for hearing
  • similar to sense organs (extrasensory bristle, chordotonal borgan) but some different structures e.g. dendritic cap
  • large extracellular structure linked to a channel in the membrane via a domain motif, then to the cytoplasm
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11
Q

How was touch observed experimentally in C.elegans?

A
  • generate (through chemical mutagenesis) then identify mutants defective for a mechanosensitive response
  • those identified were kept, bred and retested
  • genetic mapping used to characterise, clone and identify mutants: through…

recombination with the strain in which the mutations have been induced against a related strain, and mapping of the mutant phenotype for cosegregation with known markers (e.g. SNP)

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12
Q

How does the ability to sense touch help C.elegans in their natural environment?

A

Helps to escape from predatious fungi

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13
Q

What are the structural conclusions from cloning ions of C.elegan mutants?

A

The molecular model of touch

  • Mec-4 + 10: DegIENAc forms isoforms which act as pae forming units (channel normally has 2 Mec-4’s and 1 Mec-10)
  • Mec-2 + 6: accessory subunits that enable channel activity
  • Mec2: stomatin like protein on the inner leaflet of the membrane
  • Mec-6: paraoxonase like transmembrane protein
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14
Q

What are the features of the specialised cytoskelton componetnts necessary for mechanotransduction? [drosophilla, c.elegans]

A 
ECM
-MEC-5: a collagen isoform 
-MEC-1 + 9: have multiple EGF repeats
Below membrane
Mec7 + 12: tubular monomers that form 14-protofilament microtubules
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15
Q

What anchors mechanosensitive channels to the ECM, and what are the features of these channels? [drosophilla, c.elegans]

A
  • ECM proteins
  • probably Na+ gated (potentially also K+)
  • when exposed to movement will generate an action potential by shifting and therefor being gated
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16
Q

What part of the mechosensitive channel is directly involved in the gating mechanism? [drosophilla, c.elegans]

A

-the cystein rich domains are involved in the gating mechanism

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17
Q

What happens if the alanine residues in mechanosensitive channels are mutated to Valine residues? [drosophilla, c.elegans]

A

If alanie residues are mutated to Val

  • the gate is always open
  • leading to neurodegeneration
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18
Q

What is the model of mechanotransduction? [drosophilla, c.elegans]

A

Mechanotransduction involves:
a molecular assembly linking ECM to ion channel, which is linked to microtubules in the cytoskeleton
-movement gates the channel

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19
Q

What are other ways mechanosensitive channels can be activated? [not all channels are gated by mechanical deflection] And which channels use these mechanisms? [drosophilla, c.elegans]

A

TRP channels:
throught to be activated by many mechanisms that change the shape of the membrane to gate the channel
-membrane deformation: via pressue (pushing down on membrane), cell swelling or stress within the membrane itself
-2nd messengers: signals from other recpetors/channels activate these TRP channels
-biochemical deformation: 2nd messengers alter the bilayer composition, and potentially the phospholipds themselves

20
Q

What are the features of mammalian touch?

A
  • via hair structures
  • different types of hairs with different neurons
  • have lanceolate endings, merkel cell-neurite complexes, rufflini endings and free nerve endings that innervate the skin
  • different receptors have different neuronal outputs (classified via these outputs through electrophysiological recording)
21
Q

What are the neuronal outputs of the different receptors involved in mammalian touch?

A 
Lanceolate ending:
-down hair (Neurotropin-4 dependent)
-Rapidly adapting 
Free nerve endings:
-C-fibre (RunX1 or TrkA dependent)
Merkel cell-neurite complexes:
-Slowly adapting type 1 (Atoh1 and TrkC-dependent)
Pacinian corpuscle:
-rapidly adapting
22
Q

What are the features of the different neuronal outputs involved in mammalian touch?

A

Rapidly adapting:
-apply stimulation, sudden signal, then shuts off
Slow adapting:
-found all throughout skin, keep firing to long time (type I specifically innervate some hair cells)
-stretch receptive
-irregular fibre pattern during sustained pressure
C-fibre:
-slow transduction , not a strong signal (fibre has a small diameter)
Down hair:
-basket like structure around the hair itself
-sensitive to light touch

23
Q

What are the different classes of molecular channels and associated proteins in mammalian mechanosensastion?

A
  • tranduction channels
  • stomatin-like proteins
  • Voltage gated K+ channels
  • Voltage gated Na+ channels
  • Two pore K+ channels
  • TRP channels
  • Acid-sensing ion channels
24
Q

What is the mechanism of mechanotransduction in mammals?

A
  • transduction channels convert force into receptor currents
  • these trigger action potenials by opening voltage gated Na+K channels
  • this signal travels to the brain to alert the organism to the force of the stimuli

Also dictated by ion channels that signal or set the membrane excitability (Two-pore K+ channels, TRP channels, acid sensing ion channels)

25
Q

What is the function of stomatin domain proteins in mammalian mechanotransduction?

A

alter touch sensitivity in some mammalian sensory neurons by attaching to channels

26
Q

What are Piezo ion channels?

A
  • family of ion channels involved in mechanotransduction
  • can generate current in mechanically deflected membrane alone
  • 2 genes in mammals
  • 1 gene in drosophila (mutants very sensitive to touch)
27
Q

How was the function of Piezo ion channels identified experimentally?

A
  • piezo proteins expressed in non mechanosensitive cells
  • current generated by pressure
  • piezo mutants are less sensitive to mechanical touch
  • if no piezo protein, there was no response to the pressure
28
Q

How was the functional organisation of cutaenous low-threshold mechanosensory neurons identified experimentally?

A

3 different types in mammals

  • took promotor of a protein present in neurons at the start of dw e.g. ret
  • linked to GFP and created a transgeneic mice
  • fluorescence showedd where ret is expressed,
  • > can visually correlate anatomy with electrophysiology
29
Q

What are the classes of low threshold mechoreceptors?

A
  • Classified as Aβ, Aδ, or C LTMRs

- based on the conduction velocity

30
Q

What are the features of C-LTMRs?

A
  • slow adapting
  • small diameter
  • slow conduction velocities
  • respond to radipdly cooling
31
Q

What are the features of Aβ-LTMRs?

A
  • rapid conduction velocities
  • radily adapting responses to mechanical stimuli
  • very sensitive
32
Q

What are the features of Aδ-LTMRs?

A
  • very sensitive mechanical properties
  • rapid adaptation
  • slow conducting velocity
  • respond to cooling
33
Q

What are the features of hair cell types associated with LTMRs?

A
  • 3 main hair cell types: guard, zigzag, and awl/auchenne
  • each innervated by uniquie combinations of Aβ, Aδ, or C LTMRs
  • always the dorsal horn of the hair that is innervated and conveys the quality of touch
  • Aβ-LTMRs form lancedate nerve endings and assocaited with 70% awl/auchenne hairs and 30% zigzag hairs
  • Aδ LTMRs form LE and are associated with 70%zigzag and 30%awl/auchenne
  • can have slight differences in the structure and this helps to mix the anatomy - increasing the sensitivity of transduction
34
Q

How do hairs transduce qualities of touch sensation?

A

There are a number of different ways
1- rel numbers and distribution of hairs result in their deflectional properites
2-unique conmbinations of LTMRs associated with hair types
3-distinct sensitivities, conduction velocities, spike train pattern and adaption properties of the 4 main LTMRs
-information integrated in dorsal horn to convey complexity of touch sensation

35
Q

What are the combinations of LTMRs in guard hairs, zigzags, Awl/auchenne?

A 
Guard hair cell
-Aβ (rapid and slow response)
Zig zag
-C-LTMRs
-Aδ LTMRs
-Aβ LTMRs
Awl/auchenne
--Aβ LTMRs
-Aδ LTMRs
-C-LTMRs
36
Q

What are the features of sound transduction and hearing? (bit shit question)

A

-vibration of an object causes surrounding air to condense and vibrate
-forms waves that travel at 700mph
-humans detect frequences of 30-20,000HZ and amplify by 100X
-differences in the physical dimensions of amplitude(loudness), frequency(pitch) and complexity(timbre) result in differences in the perceptual dimensions
2 ears allow to detect WHERE sound is
-ear can differentiate sounds to detect individual component frequencies of a complex sound to identify the nature of that particular sound

37
Q

What is the anatomy of the human ear?

A
  • outer ear made up of: pinna (ear canal) and tympanic membrane (hooked up to 3 bones - ossicles)
  • Inner ear made up of: hollow region behind the tympanic membrane, contains the 3 ossicles
38
Q

How si sound transmotted through the anatomy of the ear?

A
  1. Sound channels down the ear tunnel to the tympanic membrane which is connected to the ossicles
  2. Movement of the tympanic membrane moves the ossciles, and the stapes bone connects to the oval window of the cochlea, causing movement in the cochlea fluid (Round window prevents compression)
  3. Movement in the bascilar membrane and the tectoral membrane causes defection of hair cells within the compartments of the cochlea (Parts of the cochlea are tuned to frequency - regions closer to the ossicles respond to high frequency)
  4. Deflection of hair bundles in the direction of the longest stereocillia triggers the tip link leading to the opening of MEK transduction channels at the lower end of tip links
  5. In fast adaptation, Ca enters the transduction channel and binds near or on the channel and causes channel closure
  6. In slow adaptation, the adapter motor at the upper end of tip links detaches from the actin cytoskeleton and slides down the sterocillium, leading to the release of tension in the transduction machinery (slipping phase of slow adaptation). Then the motor complex climbs up the sterocillium, reestablishing tension (climbing phase of slow adapation)
39
Q

How is the ear tuned to different frequencies?

A

by:

  • height of sterocilla and width and thickness of basilar membrane
  • movement of membrane causes membrane depolarisation and convert the vibration to an action potential
40
Q

What genes in mice are linked to our understanding of hair cells in hearing (identified through hearing loss)?

A

headbanger, deaf circular, waltzer

41
Q

What is the structure of the hair bundles involved in hearing?

A
  • extracellular filaments connect stereocillia and kinocilium into a bundle
  • tip links project in axis of mechanical sensitivity of hair bundle
  • potentially gene transduction channels in the stereociliary tips
  • components sit on shift plate, allowing them to swing back and move
42
Q

What occurs from damage of the tip links of hair cells involved in hearing?

A

loss of mecanical sensitivity

43
Q

How do hair bundles function in mechanotransduction of sound in the ear?

A
  • deflection of hair bundles in direction of stereocillia leads to the opening of transduction ion channels at the lower ends of tip lips
  • Ca2+ enters the transduction channel and binds to the channel or a site near it and facilitates its closing (fast adaption)
  • Adaptation motor (myosin motor protein) at the upper end of tip links subsequently detaches from the from the actin cytoskeleton and slides down stereocillium so that tension is released in the transduction machinery
  • motor complex then climbs up the stereocillium resetting the tension
44
Q

What are the main features of mammalian hearing?

A
  • sound is channeled to the tympanic drum to generate movement of stapes
  • movement of stapes generates oscillation of oval window, causing movement of the fluid in the cochlea (round window prevents compression at this stage)
  • hair cells are tuned to the frequency of the vibration of the fluid in the cochlea
  • movement of the basiliar membrane and techtorial (?) membrane causes deflection of hair cells
  • the actinmyosin cytoskeleton within the hair cells is critical for its function and the triggereing of the tip link to gate the firing of the hair cell to an action potential
45
Q

What is the mechanism of insect hearing?

A

-via johnstons organ (segment 2 of the antenna)
-sound causes vibration which causes antennal rotation in the arista, and stretching of the cap
-stretch receptors detect ‘noise’ through feedback actions of TRP channels in cillum inducing an action potential
nompC - TRPN - promote feedback - mutants no neuronal activity
iac, nanchung -TRPV - promote feedback gain - mutants ‘deafened’, overactivity

46
Q

How was the function of the johnstons organ determined experimentally?

A

-made lots of mutatns and screened for deaf insects
How?
Drosophila males sing courtship song, which females respond to
-when played artificially, male drosophila pick up the song and begin to sing it as well
-if do not join in = deaf
Found:
nompC - TRPN - promote feedback - mutants no neuronal activity
iac, nanchung - TRPV - promote feedback gain - mutants ‘deafened’, overactivity
TRP receptors are central to mechanosensitive response in insects

Neuroscience (12 decks)

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