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BMS3 > Sensory Neuroscience > Flashcards

Sensory Neuroscience Flashcards

1
Q

The auditory system can detect sound induced displacement up to what unit

A

picometer

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2
Q

Auditory system can hear frequencies between…

A

20-20,000 Hz

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3
Q

Sound in space is detected due to … between the 2 ears

A

microsecond differences in sound arrival

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4
Q

The auditory system displays a …. fold acoustic power. From a pin drop to jet engine

A

trillion

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5
Q

There are around …. people in the UK with hearing loss

A

11 million

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6
Q

More than …% over the age of 50 have hearing loss. This rise to …% of people over 70

A

40% of 50yo.

71% over 70

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7
Q

Sensory transduction converts sensory information into…because the brain only understands this.

A

electrical activity

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8
Q

All sensory receptors are transducers of different..

A

modalities (of stimulus)

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9
Q

A stimulus move the hair cell bundle which results in..

A

opening of channels and change in membrane permeability. K+ cause depolarisation.

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10
Q

Sensory receptors transmit 4 types of information:

A

Modality
Location
Intensity
Duration

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11
Q

Modality means the..

A

quality and nature of sound - what type of information

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12
Q

Location of a sound is done by..

A

interaural timing and intensity differences. Most species use a combo.

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13
Q

Large receptive fields allow sensory cells to detect stimuli over a ….area but with less…

A

Wider area, less precision

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14
Q

Intensity of sound is processed by..

A

increased firing frequency.

increased recruitment of neurons

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15
Q

Duration of sound is detected by..

A

Tonic receptors - slow adaptation, respond continuously, persistence.
Phasic receptors - burst, fast adaptation

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16
Q

Sound works by compressing patches of air, increasing pressure. When an object moves away air is…

A

rarefacted, decreasing pressure

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17
Q

Frequency is the number of…

A

compressions of air that pass our ears in 1 second (cycles per second)

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18
Q

Intensity of sound is the difference in..

A

pressure between compressions and rarefactions.

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19
Q

Human hearing range decreases significantly with…

A

age and exposure to noise

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20
Q

sensory perception consists of…

A

stimulus, transducer, brain

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21
Q

The cochlea is filled with … which causes …% of sound energy to be reflected

A

Fluid cause 97% of energy to be reflected. It takes up much more energy for sound to travel through air

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22
Q

Sound travelling through air is reduced by fluid-filled cochlea and the … They transfer energy as … energy

A

ossicles of the middle ear allow sound energy to be transferred as mechanical energy

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23
Q

The stapes attaches to the… which causes movement of fluid in the cochlea

A

oval window

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24
Q

Vibrations of the ossicles vibrate the…

A

tympanic membrane

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25
Q

The tympanic membrane has an area … fold greater than the oval window. This amplifies mechanical energy to the…

A

20 fold greater. Amplifies energy from the tympanic membrane to the oval window

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26
Q

The malleus and incus act to…

A

amplify sound waves

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27
Q

The outer ear is called the … and its shape helps to collect sounds from..

A

The pinna collects sounds from a wide area

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28
Q

The auditory canal ends at..

A

the tympanic membrane/eardrum

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29
Q

The cochlea contains apparatus to transform …. into ….

A

physical motion of the oval window into neuronal response

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30
Q

Neuronal output from the cochlea is transferred and processed by…(4)

A

nuclei in the brainstem.
relay in thalamus.
mediate geniculate nucleus.
primary auditory cortex.

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31
Q

The size difference of tympanic membrane and oval window affects pressure, how?

A

Pressure exerted on the oval window is greater, sufficient to cause fluid movement in the cochlea

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32
Q

At the base of the cochlea, there are 2 membrane covered holes:

A

round window and oval window

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33
Q

The tube of the cochlea (inside) is divided into 3 fluid-filled chambers:

A

Scala vestibuli.
Scala media.
Scala tympani.

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34
Q

Reissner’s membrane separates…

A

scala vestibuli and scala media

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35
Q

The basilar membrane separates..

A

scala tympani and scala media

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36
Q

On the basilar membrane is the ….. which contains auditory receptor neurons

A

Organ of Corti

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37
Q

On top of the organ of Corti is…

A

the tectorial membrane (collagen structure)

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38
Q

At the apex of the cochlea, the scala media …. and the scala vestibuli and tympani…

A

Scala media closes off.

Scala vestibuli and scala tympani join - continuous with one another.

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39
Q

Fluid in scala vestibuli and scala tympani is called..

A

perilymph

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40
Q

perilymph has a silimar ionic content to..which is…

A

CSF - low K, high Na

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41
Q

Fluid in the scala media is called..

A

endolymph

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42
Q

endolymph has ionic content of:

A

high K, low Na. Like intracellular fluid

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43
Q

…lymph surrounds stereocilia bundles and …lymph surround the rest of the hair cell

A

Endolymph surrounds sterocilia.

Perilymph surrounds rest of hair cell.

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44
Q

Ionic content differences are generated by active transport at the..

A

stria vascularis (endothelium lining of scala media)

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45
Q

Endolymph has a potential … more positive than perilymph

A

80mV

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46
Q

The basilar membrane is wider and stiffer at the… than at the base.

A

Wider and stiffer at the apex of the cochlea

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47
Q

High frequency sounds cause vibrations of the basilar membrane closer to the … Low Hz sounds cause vibrations at the…

A

High Hz = base of cochlea

Low Hz = apex of cochlea

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48
Q

Specific frequencies activate specific portions of the basilar membrane. Cochlea is a …

A

frequency analyser

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49
Q

Sound displaces the basilar membrane during compression by..

Stapes -> basilar membrane

A

Stapes moves inwards = inwards mov of oval window.
Increase of pressure of scala vestibuli causes fluid movement in opposite direction in scala tympani.
Causes outwards mov of round window = downwards mov of basilar membrane.

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50
Q

During rarefaction, sound displaces the basilar membrane by..

A

Stapes moves outwards = outwards mov of oval window.
Decrease in pressure in scala vestibuli. Mov of fluid in scala tympani causes inwards mov of round window. Basilar membrane moves upwards.

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51
Q

One hair cell has …. stereocilia extending from their top

A

1000

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52
Q

Sterocilia detect displacements of the….to what unit?

A

Basilar membrane. nanometers

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53
Q

Hair cells are sandwiched in between…

A

basilar membrane and reticular lamina

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54
Q

When the basilar membrane move up (rarefaction), stereocilia bend…

A

outwards - towards taller sterocilia

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55
Q

During compressions, the basilar membrane moves…and stereocilia move…

A

basilar membrane moves down and stereocilia move towards the shorter ones

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56
Q

Stereocilia move as a unit due to..

A

cross link filaments

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57
Q

On the tips of stereocilia, there are cation channels connected to..which are connected to…

A

elastic filaments called tip links which connect to the adjacent cilium.

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58
Q

When stereocilia are straight, tip link tension holds the channel…allows for..

A

partially open (10-20%). This allows for a small leak of K into the hair cell.

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59
Q

When stereocilia is moved by basilar membrane moving upwards, tip link tension…causing..

A

increases. This causes the channel to be opened further, increasing the inward K current into the hair cell.

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60
Q

Compressions causes tip link tension to..

A

be relieved. This closes the channel completely so no K+ moves into the hair cell.

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61
Q

Entry of K+ into the hair cell causes..

A

depolarisation. Activates Cav channels. Influx of Ca releases NT, activating SGN.

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62
Q

Reptiles have …. hair cells, with common afferent and efferent innervation.

A

a single class type of hair cell

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63
Q

Mammals have 2 types of hair cell. Inner hair cells contact … fibres. Outer hair cells contact…fibres

A

IHCs contact the majority of afferent fibres.

OHCs have strong efferent innervation

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64
Q

Inner hair cells are the primary..

A

sensory receptors

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65
Q

95% of afferent SGN innervates..by 1:1 ratio. This enhances..

A

IHCs.

Frequency resolution

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66
Q

5% SGN innervate the… One SGN fibre innervates…

A

OHCs. One fibre innervates numerous cells.

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67
Q

Each hair cell is … in diameter

A

10 micrometers

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68
Q

As sound intensity rises, ….decreases.

A

Sensitivity decreases

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69
Q

Cochlear output is from…

A

IHCs

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70
Q

The role of OHCs is to..

A

amplify mov of the basilar membrane during low intensity sounds to enhance sensitivity

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71
Q

Hair cells develop as many….with one…

A

microvilli (undifferentiated projections) with one kinocilium

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72
Q

In embryonic stages, the kinocilium…

A

migrates laterally to define polarity

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73
Q

After the kinocilium migrates, microvilli start to…

A

elongate and form stereocilia of graded heights

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74
Q

Short stereocilia grow up to …. post natally

A

5 days

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75
Q

Long stereocilia grow up to…. post-natally

A

12 days. This corresponds to the onset of hearing.

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76
Q

Stereocilia within a hair bundle are organised..

A

in rows of decreasing height

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77
Q

In mammals, the kinocilium is present…

A

only in development - degenerates after birth

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78
Q

In development, mechanotransduction occurs before..

A

mature bundle formation and onset of hearing. Increased Ca influx cause by MET could be important for stereocilia development

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79
Q

Stereocilia are supported by bundles of…

A

polarised actin filaments - cross-bridged with fascin1 and plastin2

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80
Q

Tip links are composed of..

A

stereocilin, complex of homodimers: cadherin23 and protocadherin15

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81
Q

Stereocilia get … as they insert into the hair cell membrane. This allows for…

A

Narrower. This allows for movement without bending. Actin filaments do not extend to this part to reduce stiffness

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82
Q

To maintain constant length of stereocilia, rates of … and … are coordinated

A

Actin polymerisation and depolymerisation

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83
Q

Actin binding proteins are involved in stereociliary growth and are:

A

Eps8

Eps8L2

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84
Q

Which hair cells are attached to the tectorial membrane?

A

OHCs

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85
Q

Planar cell polarity of hair cell bundles ensures a…

A

coordinated response

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86
Q

Eps8 is found mainly on..

A

tips of taller stereocilia

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87
Q

KOs of Eps8 show..

A

dysregulation of height and no. of rows

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88
Q

Eps8L2 is found on..

A

shorter stereocilia

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89
Q

KOs of Eps8L2 show..

A

no change except for matured heights.

Progressive hearing loss due to less coupling of stereocilia to the tectorial membrane

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90
Q

Cochlea and MET is studied in vitro by..(2)

A

electrophysiology.
2 photon imaging.
Sounds waves delivered to cochlear tissue on mesh by pipettes.
Use whole cell patch clamp recordings

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91
Q

Turtles have stereocilia which:

A

Have lots of rows, meaning greater adhesion and mroe MET channels.
Good for detecting low frequency stimuli

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92
Q

Bat IHCs have:

A

2 rows of stereocilia with lots of space in between.
This reduces resistance between hair cells, allowing them to move very fast.
Good for detecting high frequencies.

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93
Q

Hair cells show adaptation which is:

A

a decrease in response to a constant stimulus - can be slow (<100ms) or fast (<10ms)

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94
Q

Adaptation allows for:

A

Operating range to be reset in hair bundle.
Maintains sensitivity.
Prevents saturation.

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95
Q

The MET channel is non-selective for cations, it mainly transports..

A

K+

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96
Q

Ca interacts with the MET channel by..

A

binding to the channel pore and blocking it, causing fast adaptation

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97
Q

…hair cells have synaptic ribbons

A

IHCs

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98
Q

…hair cells have postsynaptic cisterns

A

Outer HCs

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99
Q

excitatory bundle deflection causes a maximum current…

A

depolarisation of -30mV in IHCs and -20mV in OHCs.

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100
Q

Cadherin23 of tip links is bound to…(3)

A

Myosin7a, Harmonin-b and Sans

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101
Q

Mutants of cadherin23 show..

A

loss of tip links

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102
Q

Mutations in tip link proteins are involved in..

A

Usher’s syndrome - deafness and blindness

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103
Q

MET currents are difficult to measure in mammals because..

A

the kinetics are much faster than in non-mammalian hair cells

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104
Q

MET currents are measured in vitro by using different..

A

amplitudes and measuring peak transducer currents, generating a current displacement curve.

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105
Q

Slow adaptation is cause by calcium…

A

causing myosin motors to slip on actin filaments - reducing tip link tension, closing some MET channels

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106
Q

Normally, myosin interacts with actin filaments in order to… how?

A

myosin climbs up actin filament to maintain tension in the tip link

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107
Q

Proteins of the MET channel are recently being studied in..

A

KO mice - TMC1, TMIE and LHFPL5 - located on stereocilia tips, cause deafness

108
Q

Loss of TMC1 in the MET channel causes..

A

Deafness in mice. Beethoven mice show progressive hearing loss.
Also reduced Ca permeability.
Affected adaptation.
Elimination of tonotopic gradient.

109
Q

It is thought that MET channel complex (TMC, TMIE, LH) are bound to PCD15, and that the components are..

A

essential for proper function

110
Q

Low Ca during depolarisation = larger open probability of MET channel = slower adaptation. Shifts I-X relation..

A

to the left compared to high Ca

111
Q

….has shown the MET channels are at the lower end of tip links.

A

Confocal imaging of Ca induced fluorescence

112
Q

MET channel information is still unknown because:

A

Small no. of cells.

Cannot expand hair cells in vitro.

113
Q

Usher’s is a … genetic disorder characterised by.. (3) There are … types.

A 
recessive.
Bilateral deafness.
Late onset visual impairment.
Vestibular dysfunction
3 types.
114
Q

USH1 is characterised by:

A

Severe to profound deafness.
RP (retinitis pigmentosa) shows gradual narrowing of visual field apparent in childhood.
Vestibular abnormalities - sitting independently.

115
Q

USH2 is characterised by:

A

Moderate to severe deafness.
Mainly affects high Hz sounds.
No vestibular dysfunction.
RP diagnosed between ages 10-40.

116
Q

USH3 - hearing and visual loss begin during..

A

late childhood-adolescence

117
Q

Genes mutated in Usher’s 1:

A 
Myo7a
Harmonin
Cadherin23
Protocadherin15
Sans
CIB2
118
Q

All USH proteins have complex interactions with each other, meaning..

A

any mutation will affect auditory transduction

119
Q

Cadherin23 and Protocadherin15 are … dependent adhesion molecules

A

Ca

120
Q

CADH23 and PCD15 were found on tip links by..

A

antibodies for gold staining found distribution on tip link;
CADH23 was found towards the top
PCD15 found mostly towards bottom

121
Q

Analog of USH1B…

A

Shaker 1 gene in mice. Mutation arose spontaneously and these were the first mice used to model deafness

122
Q

Shake 1 gene encodes.. In the absence of myo7a…

A

Myosin7a.
Mutants have completely disorganised hair cell bundles.
Rightwards shift in displacement curve - requires twice as much displacement to open the channel.

123
Q

Mutated CIB2 shows..

A

Reduced organisation.
Over elongation.
Loss of function - gradual degeneration.
Complete loss of MET channel

124
Q

….screens showed that CIB2 interacts with TMC1. Interaction is lost in mutants

A

Yeast 2 hybrid screens and FRET

125
Q

type 1 SGN innervate..

A

IHCs

126
Q

type 2 SGN innervate..

A

OHCs

127
Q

a type 2 SGN fibre contacts how many cells?

A

one fibre innervates 3-10 outer hair cells

128
Q

SGN fibres are…

A

afferent

129
Q

Type 2 fibres are … activated and need … of stimulation

A

weakly activated - need a lot of stimulation. Not well understood

130
Q

Ribbon synapses form between … and…

A

IHC and SGN type 1 fibres

131
Q

Conventional synapses form between … and …

A

OHC and type 2 SGN fibres

132
Q

Ribbon synapses are present in: (3)

A

Auditory system -IHCs.
Visual system -retinal and pineal photoreceptors, bipolar cells.
Vestibular system.

133
Q

Ribbon synapses are found when transmission requires…

A

graded modulation of ongoing vesicle exocytosis

134
Q

Ribbon synapses allow sensory receptors to be tonically active but they vary… Allows for..

A

the degree of stimulation - firing rate, temporal info. This allows for precise coding across a wide range of stimulus intensities and locations.

135
Q

Disrupting synaptic ribbons impairs …. processing and…

A

temporal processing which consequently causes issues with speech recognition and sound localisation

136
Q

Ribbons are electron dense structures at presynaptic membranes. Its major component is …. which is anchored to the membrane by…

A

RIBEYE is anchored to the presynaptic membrane by Bassoon. This prevents structures from floating in the cytoplasm.

137
Q

Ribbons contain proteins:

A

Rim1 - vesicle priming.
KIF2A - kinesin motor complex.
Piccolo - cytomatrix active zone.
GCAP2 - Ca binding protein.

138
Q

Ribbons can have different shapes: … and there can be 20-400 vesicles present

A

spherical, planar or oblong

139
Q

In mammalian hair cells, ribbons are … in width. Non-mammalian ribbons are … in width.

A

Over 200nm in mammals.

200-400 nm in non-mammals.

140
Q

Ribbons are closely linked to Cavs. There are …. channels per ribbon so that there is short diffusion distance.

A

100-200 channels per ribbon, although this varies - differential sensitivities, threshold and dynamic ranges.

141
Q

There are 3 types of vesicle at a ribbon synapse:

A

Readily releasable - closest to membrane.
Secondary pool - resupply.
Cytoplasmic pool - resupply.
Rapid and continuous/sustained depolarisation.

142
Q

Ribbons studied by confocal microscopy, using antibodies against… What was seen?

A

RIBEYE and GluR2. There is tonotopic distribution from apex to base, with high levels of synapses at a particular Hz range. This gives high sensitivity at these Hz

143
Q

Synaptic vesicles are prepared for use. First:

A

Vesicles are primed so they are Ca responsive.
Ca mediates vesicle fusion involving SNAREs (not ribbons).
In ribbons, Ca is sensed by Otoferlin.

144
Q

Otoferlin mutations cause..

A

reduced exocytosis in IHCs, despite vesicles accumulating at the active site. Causes deafness.

145
Q

Ca sensors of synaptic vesicles also include:

A

Synaptotagmins

Syt1, Syt2

146
Q

Development of synaptic machinery has been studied in … since systems are very well conserved

A

mice and rat studies

147
Q

…weeks are needed before the cochlea can detect sound in mice

A

3 weeks

148
Q

In babies, even though IHCs cannot hear sounds, they show…important for..

A

spontaneous APs driven by Ca important for refining the tonotopic projections of the pathway.

149
Q

In development, Ca spikes are….and become…at P6

A

small and broad. They become faster

150
Q

Developmental, spontaneous Ca APs arise due to…

A

resting potential of IHCs is close to threshold of Cav activation.

151
Q

Ribbons appear later in development; appearing as …at P6, and changing to … at ….

A

Appear as spherical at P6, change to elongated at P12

152
Q

In ribbons, there is an increase of Ca current through development which then..

A

steadies out. Also seen downreg of Cav channels

153
Q

immature IHCs need Ca entry through…compared to mature IHCs

A

multiple channels - exponential relationship.

Mature IHCs have closer Cav, Ca entry through one channel is sufficient. Linear relationship

154
Q

Swtich from expontential to linear relationship of Ca entry and exocytosis increases…

A

release efficiency. Allows for maintenance of sensitivity for different intensities.

155
Q

immature IHCs show …. immunostaining

A

much more RIBEYE, Cav and GluRA2/3

156
Q

NT release is measured by..

A

capacitance - cell surface area due to vesicle fusion

157
Q

Vestibular system allows for..

A

Proprioception - body positions and movements to be relayed to the brain.
Rapid reflex

158
Q

Vestibular system works from .. to .. frequencies.

A

very low (30Hz) to high (a few kHz)

159
Q

Vestibular system works with … and … to maintain posture and balance.

A

Somatosensory and proprioceptive systems

160
Q

Visual inputs are stabilised by the..

A

vestibular ocular reflex - occurs in response to head movement

161
Q

Vestibular ocular reflex detects head movement which relays signals to the eye muscles. This allows for..

A

eye movements in the opposite direction to head movement to keep the image in the centre of the visual field.

162
Q

vestibular ocular reflexes are the..

A

fastest in the body and are highly accurate

163
Q

Vestibular hair cells are contained in..

A

interconnected sets of chambers called labyrinths

164
Q

Vestibular labyrinths have 2 structures with different functions:

A

Otolith organs - orientated at right angles, detect linear acceleration of head.
Semicircular canals - ant, post, and horizontal, sensitive to angular acceleration (x, y, z axes)

165
Q

Semicircular canals are sensitive to..

A

changes in velocity - not just velocity

166
Q

Otolith organs are:

A

saccule and utricle

167
Q

Vestibular hair cells make excitatory synapses with..

A

a sensory fibre of the vestibular nerve

168
Q

Sensory organs of the saccule and utricle are… It differs in the organs by..

A

sensory epithelia called macula. In the saccule it is vertical, in the utricle it is horizontal.

169
Q

Macula are orientated differently so that..

A

linear acceleration in all directions can be detected.

170
Q

Macula supporting cells have cilia (which bend) projecting into a ..

A

gelatinous cap - this adds weight to the membrane so that otolith organs respond to gravity.

171
Q

The utricle and saccule are mirrored on each side of the head so that when hair cells on one side are excited…

A

hair cells on the other side tend to be inhibited.

172
Q

Semicircular canals detect angular acceleration which is..

A

generated by sudden rotational movement

173
Q

Hair cells of semicircular canals are clustered within a sheet of cells called … located in a buldge along the canal called..

A

Crista are located in the ampulla

174
Q

Cilia of crista project into gelatinous cupula which span the lumen of the canals within… What does this do?

A

the ampulla. This synchronises movement of hair cells

175
Q

Hair cells in a given ampulla are in the…

A

same direction - all get excited or inhibited together

176
Q

There are 2 types of vestibular hair cells:

A

Type 1 - tear drop shape, calyx nerve endings which surround 1-3 VHCs.
Type 2 - columnar, afferent boutons, provide slower graded responses

177
Q

Some VHCs are contact by..

A

both calices and afferent boutons

178
Q

VHCs differ to IHCs and OHCs because:

A

Longer bundles.
More rows.
Stereocilia vary greatly in length (steep staircase).
Kinocilium present but not functional

179
Q

Slow adaptation in VHCs is dependent on..

A

Myosin 1c - mutations show complete loss of slow adaptation

180
Q

There is a large proportion of slow adaptation in VHCs due to..

A

greater no. of rows of stereocilia

181
Q

VHCs have …. ribbons per cell

A

6-20

182
Q

Alcohol causes vertigo and oscillopsia by..

A

altering the density of the gelatinous membranes

183
Q

The lateral line is seen in … It is located…

A

All aquatic vertebrates. It is located on the surface of the entire body, seen as series of dots.

184
Q

Units of the lateral line are called..

A

neuromasts.

185
Q

Neuromasts contain … and … cells which are innervated by..

A

Hair cells and supporting cells are innervated by both afferent and efferent fibres

186
Q

Aquatic vertebrates detect auditory and vestibular stimuli such as:

A

Sound waves in water.
Pressure gradients in water.
Movement.
Allows for schooling, escape, sexual courtship and predation

187
Q

In Zebrafish, the lateral line has 2 major branches:

A

Anterior - around the head.

Posterior - length of trunk and tail.

188
Q

Zebrafish has … semicircular canals, with anterior and posterior maculae

A

3 semicircular canals - angular acceleration.

Maculae - linear acceleration and gravity.

189
Q

Weberian ossicles connect to the … and …

A

Saccule and swimbladder

190
Q

The swimbladder compresses gas which cause oscillation. This…

A

amplifies sound delivered to the saccule

191
Q

The lateral line is functional … post fertilisation since it is critical for survival

A

48 hours post fertilisation.

Starts at 20 hours pf

192
Q

Zebrafish are an attractive model organism for studying hair cells because..

A

Less time to wait for development.

Zebrafish are good transgenic tools.

193
Q

The lateral line emerges from a … called prim1. This deposits … and … along the body of the fish at..

A

Primordium. This deposits 5 clusters of hair cell groups and growth cones of axons, and a continuous stripe of interneuromast cells during P1-5.

194
Q

Lateral line hair cells are stimulated..

A

directly

195
Q

The cochlea is highly sensitive and specialised but this come at a cost:

A

Loss of regenerative ability.

Need stimuli amplified.

196
Q

Lateral line hair cells on the surface allow for..

A

a much quicker response and detection of stimuli from any direction.

197
Q

How is the auditory system scaled in aquatic vertebrates?

A

The lateral line is larger depending on the size of the fish, but the size of hair cells is the same - there are just more

198
Q

Neuromasts differ from mammalian hair cells as…

A

They have a kinocilium.
Neuromast stereocilia look more like VHCs.
Neuromasts are embedded in a cupula

199
Q

Neuromasts can respond to stimuli from all directions because their neuromast hair cells…

A

show direction polarity - respond in all directions

200
Q

Afferent fibres of neuromasts innervate many hair cells of/from…

A

one polarity. This means only one set of fibres will be excited by a stimulus coming from a particular direction.

201
Q

1 neuromast is innervated by … afferent neurons

A

8 neurons

202
Q

Long stereocilia would cause..

A

reduced stiffness - too floppy. Bending at the top instead of base to a stimulus. Would reduce sensitivity.

203
Q

Mutation of CADH23 in Zebrafish specifically impacts..

A

mechanotransduction

204
Q

Zebrafish have a duplication of TMC2, a … would be required to study TMCs

A

triple KO

205
Q

LHFPL5 Zebrafish mutants show..

A

deafness and deficits in balance. Also seems to be important for localisation of PCD15

206
Q

At higher Hz, IHCs are unable to encode info and show a sustained response. OHC help by…

A

feedback on IHCs to stimulate them more

207
Q

Type 1 SGN neurons are … and travels to the…

A

Myelinated, bipolar and unbranched. They travel to the cochlea nucleus in brainstem

208
Q

More than 1 type 1 SGN fibre to each IHC means that..

A

the signal is split into different streams - they remain segregated along the pathway to allow IHCs to encode more info. Also, if 1 fibre is damaged, IHC doesnt lose all function.

209
Q

Apically, SGNs have:

A

Prologened latency.
Slow onset time
Longer AP duration.
Greater density of presynaptic proteins

210
Q

Basally, SGNs have:

A 
Short latency (by Kv channels).
Increased expression of postsynaptic receptors AMPA, GluR2/3
211
Q

Type 2 SGNs are branched and… They contact up to…

A

unmyelinated. 30 OHCs

212
Q

Function of type 2 SGNs is not known. They seem to response only when..

A

All contacted OHCs are activated - perhaps for damage/overstimulation feedback - nociception

213
Q

LOC efferents are from the..and synapse with..

A

lateral superior olive. They synapse with Type 1 SGNs

214
Q

LOC efferent fibres may function as inhibitory. This could cause..

A

inhibition of type 1 SGNs to reduce excitotoxicity

215
Q

MOC efferents are from the…and form ….synapses with OHCs

A

medial superior olive. They form large inhibitory synapses with OHCs. This reduces cochlea amplification to prevent damage.

216
Q

Afferent fibres leaving the cochlea form 2 pathways:

A

Dorsal - sound localisation, bypasses superior olive

Ventral - encoding sound

217
Q

The superior olive receives input from both cochlea in order to…

A

encode interaural time and level differences for sound localisation

218
Q

What does the inferior colliculus do?

A

Combines cochlear input with somatosensory and visual centres for multimodal processing

219
Q

The mediate geniculate nucleus is involved in…

A

memory and learning

220
Q

Primary auditory cortex has roles in…

A

decisions, cognition and memory

221
Q

Staggered firing of multiple neurons on successive cycles along with….allows for complete encoding of a sound

A

When staggered firing is summated, there is complete encoding called phase locking.

222
Q

The ability to phase lock is lost above…

A

2kHz - IHCs cannot encode very high frequencies

223
Q

Intensity is encoded by:

A

No. of neurons - more fibres firing = louder sounds.

Spike rate increasing until it saturates

224
Q

3 forms of hearing loss occur by:

A

Auditory processing disorder - brain
Conductive - outer and middle ear
Sensorineural - cochlea and auditory nerves

225
Q

ABR is response to repetitive acoustic stimulation recorded from…

A

scalp EEG. Has 5 peaks. Wave 1 is called the compound action potential

226
Q

DPOAE are distortion product otoacoustic emission. They are used to test…

A

function of OHCs by the vibrations of the basilar membrane

227
Q

Neuropathies can occur due to problems in:

A

IHC NT release.
Spike generation in SGNs.
Propagation of spikes along SGNs.
Transmission from SGN to cochlea nucleus

228
Q

Synaptopathies of hair cells are caused by:

A

Genetics - genes related to ribbon function, NT release, Ca current
Acquired - noise-induced hearing loss, age, chemicals (antibiotics, cancer drugs)

229
Q

Inherited mutation in OTOF gene causes…

A 
Otoferlin inactivation and non-syndromic hearing loss.
Absent exocytosis (Ca triggered)
230
Q

VGluT3 mediates vesicular glutamate uptake at IHC synapses. Mutations cause…

A

dominant hearing loss.

mental and motor retardation in some individuals.

231
Q

Cav1.3 makes up 90% of Ca current in hair cells. Important for…

A

triggering vesicle exocytosis - reduced ribbons and postsynaptic receptor clusters

232
Q

Mutations in CACNA1D cause..

A

syndromic deafness and sinoatrial node dysfunction

233
Q

Permanently damaging levels of sound are over… They cause damage to:

A

140 dB. Damages stereocilia, nerve fibres, and causes thresholds to shift.

234
Q

Temporary damaging levels of sound are about …dB. They cause..

A
  1. They cause a temporary shift in thresholds by glutamatergic excitotoxicity in IHCs.
    Can lead to hidden hearing loss (struggling to hear in noisy environments) - not detected in standard hearing tests
235
Q

In hidden hearing loss … dendrites are affected

A

afferent terminal dendrites of low spontaneous rate

236
Q

With age, synapses between … and … are lost before hair cells are affected

A

SGN and IHCs

237
Q

Potential therapies of hearing loss is injection of … into the round window, 24h after noise exposure. What would this do?

A

NT3 - neurotrophic factor. This restores synapse number and hearing function.

238
Q

Transfection of VGlut3 by AAV into the round window can do what..

A

restore expression of VGlut3. Shows restored ABR thresholds for 7 weeks. However, does not improve SGN

239
Q

AAV transfection of otoferlin (in 2 parts) in DFNB9 mice was injected into the round window. What happened

A

After 4 weeks, mice showed complete restoration of ABR threshold

240
Q

Hair cells are derived from prosensory cells in the…

A

cochlea duct - ventral side of the otocyst

241
Q

Cells of the early otocyst express….to remain undifferentiated

A

Jag1, Sox2, Notch, Wnt and FGF

242
Q

At E….. p27 is upregulated and causes…

A

E12-14. P27 inhibits cell cycle and stops division so cells can divide

243
Q

At E14, cells become sensory hair cells by expression of…

A

ATOH1, Wnt and FGF

244
Q

At E14, cells become non-sensory cells through expression of..

A

Hes1, Hes5 and FGF

245
Q

At E9-10, otocyst cells migrate to form…

A

Neurons - through expression og Ngn1 and NeuroD

246
Q

At E17, the inner ear….

A

is fully formed

247
Q

p27 is expressed in a …. gradient. This means that cells exit cycle at different times and cells which are last to exit….

A

Longitudinal gradient. Cells which exit cell cycle last differentiate first

248
Q

ATOH1 KO mice fail to…

A

produce hair cells

249
Q

Inner and outer HCs are only differentiated.. Which matures first?

A

after birth. OHCs mature before IHCs

250
Q

MET channel and mechanotransduction occurs..

A

post natally - 4 days before onset of hearing

251
Q

miRNA96 is important for determining..

A

cell fate and development in the inner ear

252
Q

miRNA96 is expressed until p5 in … and p14 in …

A

p5 in cochlear hair cells and p14 in SGNs

253
Q

A singular base change in miRNA96 in mice and humans causes

A

non-syndromic progressive deafness

254
Q

Mutant miRNA96 mice show:

A

Thinner stereocilia.
Reduced surface area.
OHCs are shorter but normal arrangement of HCs. - development up until birth is normal

255
Q

After birth of mutant miRNA96 mice, what is shown?

A 
Early onset hearing deficits.
IHCs show retention of Ca APs.
IHCs fail to acquire K channels.
Altered synaptic development.
Immature IHCs
256
Q

miRNA96 is crucial for…

A

functional differentiation and maturation after birth

257
Q

Electromotility is the ability of OHCs to change their length in response to stimulus. This requires…

A

motor protein - prestin.

258
Q

Mutated prestin causes …. fold decrease in sound sensitivity

A

100

259
Q

Prestin reduces its area when the cell depolarises, amplifying …

A

movement of the basilar membrane

260
Q

Ikzf2 is expressed only in OHCs from p4 through to maturation. Ikzf2 encodes..

A

Helios, a Zn finger protein

261
Q

Mutations in Helios (encoded by Ikzf2) cause..

A

hearing impairment, loss of hair cell bundles, functional deficit in OHCs, early onset sensorineural hearing loss

262
Q

Cello mice are models of hearing loss, they have mutations in Ikzf2. They show highly reduced expression of prestin in OHCs meaning..

A

highly reduced electromotility in OHCs

263
Q

Immature OHCs fire …. APs very quickly. These are completely lost at P4 which corresponds to the expression of…

A

Ca driven APs. Lost when prestin in expressed.

264
Q

Immature Ca APs are important for development since..

A

they may act to trigger functional maturation of the OHCs - upreg or downreg of channels (?)

265
Q

In ARHL there is..

A 
stiffening of the eardrum.
Loss of HCs
Degen of stria vascularis
Decrease of neurons.
Decreased temporal lobe activity.
266
Q

3 techniques used to study auditory cells:

A

Fluorescence imaging.
Patch clamp electrophysiology
Optogenetics

267
Q

To see when and where events occur, studying techniques need to show..(5)

A 
high temporal resolution.
high spatial resolution.
scalability.
high sensitivity.
minimal invasiveness.

BMS3 (6 decks)

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