Auditory synapses
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- Created by: Sarah
- Created on: 23-05-19 13:08
what is the role of the sensory system?
to represent the external world
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what does sound do in mechanotransduction?
displaces the sterociliary bundle, the displacement opens the MET channel and when they are open the K and also Ca go into the bundle but K generates receptor potential
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why do we need to generate a receptor potential?
depolarisation of the cell- release NT
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why do you need to open ca channels?
depolarisation opens VG ca channels -> ca comes in triggers fusion of vesicles to M -> transmitter can activate the auditory nerve
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what needs to be encoded at the synapse for acoustic signals?
frequency, intensity and time
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what is frequency mainly determined by?
the position of the cell along the length of the cochlea (as cochlea is tonotopically roganised)
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what makes the cochlear a frequency analyser?
different properties of basilar membrane is stiff at the base by having a wider width
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what is tonotopic frequency selectivity?
tontopic map is present throughout the auditory pathway- from cochlea up to brain
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what is frequency encoded by?
position of the cell along the length of the cochlear
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what needs to be encoded in every single sensory hair cell?
intensity and time
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what is timing very important for?
sound localisation
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what is intensity important for?
discriminating the pitch of a sound
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what are afferent neurons called?
spiral ganglion neurons
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what afferent fibres innervate IHCs?
type 1 SGNs
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what afferent fibres innervate OHCs?
type 2 SGNs
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where do SGNs take info?
from the cochlea to the brain
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how much of the afferent fibre innervation of the cochlea does the Type 1 SGN make up?
95%- majority
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what arrangement are the Type 1 SGNs in with the IHCs?
1:1 dconnection with IHC and presynaptic ribbon- 1:1 connections
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how many SGNs can contact 1 IHC?
up to 20-30
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what is the remaining 5% of afferent innervation to the cochlea?
Type 2 SGNs- innervate OHCs
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how many OHCs does one type 2 SGNs contact?
1 -> 15-20 OHCs
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why do so many SGNs contact OHCs?
fibres are weakly activated so in order to be activated you need a lot of stimulation by activating a group of OHCs simultaneously to elicit an AP
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what is the type 2 fibre thought to act as?
a nociceptor for the cochlear
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why is it hthought to be a nocipetor?
in order to activate this fibre you need a lot of stimulation from a lot of OHCs- very loud stimulation and noise all the OHCs will be activated at the same time- SGN type 2 will tell brain huge amount of sound that could be damaging
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how does the brain react to being told there's a huge amount of sound?
through the efferent fibre they are cholinergic inhibitory efferent fibres which can inhibit the OHC
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what do the efferent fibres do to the OHC
reduce the mechanical activity of the cell, reduce amplification of the cochlea- dampen down the activity of the OHC to avoid damage, too much sound signal back to avoid damage
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do they think this ribbon synaptic machinery is different in IHCs and OHCs?
no
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where has most of the work on ribbon synapses been done?
on the IHCs
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where are ribbon synapses present in the sensory system?
cochlea, vestibular system, visual system (bipolar and photoreceptor cell)
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what are the functional properites of ribbon synapses?
they allow the mature sensory systems to detect and transmit tiny singals the stereocilia bundle has the ability to detect small movement less than a nm during sound stimulation
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where else is the ribbon synapse allowing the detection of tiny signals?
the photoreceptor- can detect a single photon
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what kind of converter is a mature organ?
analog-to-digital converter
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why are ribbon synapses unique?
they work tonically (Slow)- work continuously for a long period of time, they transmit graded info with high precision across a wide range of intensities
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why are ribbon synapses so good to transmit sound?
they work with high fidelity and precision across a wide range of intensities
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if you disrupt the ribbon synapse what will it is impair?
the temporal process of sound coding = affects both speech and sound localisation
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why are they an analog to digital converter?
sensory inputs are analog because they are continious, have to be converted into APS- digital signal digitalised int APs
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why is it crucial that sound is converted into APs?
for the brain to be able to perceive sound
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why are sensory inputs analog?
because they're continous
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analog to digital defintiion?
continuous sensory graded information is converted into spiking activity in auditory fibres
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where does this analog to digital converstion happen?
at the synapse
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is the receptor potential analog or digigtla?
continous signa so rec potential is graded and sustained so analgoue but converted into digital
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what does the analog to digital conversion?
the ribbon synapse
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what is a ribbon synapse?
ribbons are these electron dense structures
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what is the major component of this electron dense structure?
RIBEYE
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What gene encodes electron dense structure RIBEYE? what is this gene associated with?
CTBP2 encodes RIBEYE is a deafness gene
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what side is this ribbon electron dense structure (RIBEYE) on?
presynaptic side
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what is found with RIBEYE
bassoon protein
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what is bassoon important for?
anchoring the ribbons- without it ribbons flow int the cytoplasm, also affects hearing
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what site are ribbon synapses localised at?
vesicle release site
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what happens at the vesicle release site?
the active zone where the presynaptic vesicles are released where presynaptic meets postsynaptic
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what is the postsynaptic fibre in this case?
the auditory fibre (cochlear nerve?)
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what are ribbons colocalised to?
ca channels
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what are ribbons opposed to?
the postsynaptic glutamate receptor
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what is the main NT present in vesicles in the inner cells?
glutamate
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what are the 3 types of pools of vesicle based on?
kinetics or release of vesicles- how they fuse to M
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what is the first pool?
radio release particle- it's one close to the M, vesicles are starting to fuse to the M, it's already there in place
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what is the 2nd pool?
vesicles along this structure are not yet at the release site but are avaliable
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whats the cytoplasmic pol?
vesicles in the cytoplasm
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why are the vesicles staggered and why so many of them?
its a continuous stimulation so needs a continuous supply of vesicles = need large amount of vesicles
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how is there a tonotopic organisation of these synapses along the length of the cochlea?
there's a change in the distribution of synapses along the length of cochlea which is crucial for function
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what is the frequency where the number of functional synapses in mice and rats different to that of the gerbil?
12-16kHz for mice and rats and 1kHz in gerbils
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why is it specifically more synapses at them frequencies in different animals?
it's the most sensitive region- need a more sensitive region so the range of localisation for these animals how they communicate so if they communicate efficiently
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why do they need a larger number of synapses to communicate efficiently?
because they provide better neural sampling so they increase the ability and acuity of the info they send to the brain
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the ribons range in number per hair cell from what?
5-30
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what determines the varied shape and size of ribbon synapses?
the type of sensory organ (Auditory or retina), animal species, developmental stage and position along the cohclea
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why are the size and shape of the synapses different?
they're optimised for the job they need to do- they change so much the number of vesicles change between 40-400
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are conventional synapses digital or analog?
they are digital- all or nothing so AP drives the phasic response
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what happens at a conventional synapse?
presynaptic cell depolarised in the AP, ca current allows ca into cell, NT release but ca channel inactivates- transiently have release of vesicles linked to AP
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how are ribbon synapses analogue?
they respond to continuous stimulation, continuous depol of the cell for a very long period of time
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how does the depolarisation over a long time change the channels in the ribbon synapse?
the cell is depolarised for longer, it opens ca channels up but they stay open for the full duration of the stimulus
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why can ca channels in the ribbon synapse stay open for whole time of the AP?
the inner cell ribbon synapses expresses a particular subtype of ca channel = Cav1.3
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how does cav1.3 differ from other ca channels?
they show very little inactivation- stay open for the full duration of the stimulus
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what does cav1.3 ca channels staying open for long in the ribbon synapses mean?
continous reease of ca - causes a continuous release of vesicles for the full duration of the stimulus = sustained vesicle release
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how many APs can sustained vesicle release drive?
hundreds of APs per second at the fibres
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classical vesicle cycle for conventional synapses?
vesicles formed, they dock, priming. ca goes in, binds to ca sensor of exocytosis and NT release, synapsin 1 and 2 SNAREs fuse the vesicle to M and release NT
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how is the situation similar different with vesicle cycle in ribbon synapses?
cycle is similar but major differences- the ca sensor of vesicle fusion in the conventional synapse you see synaptintobrevin 1 or 2. But in the ribbon synapse inner cell you use otoferlin
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what is the ca sensor in conventional synapses?
synaptin (synaptobrevin?) 1 or 2
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what is the ca sensor in ribbon synapses?
otoferlin
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what gene does otoferlin encode?
a deafness gene
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what happens in the absence of otoferlin?
become deaf
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what do they think otoferlin is also important for? how is this different to conventional synapses
vesicle retrieval for endocytosis so we have just 1 molecule instead of many doing a lot of things at the ribbon synapse
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what family is otoferlin a member of?
ferlin family of membrane fusion related proteins
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what 3 things does otoferlin do?
1) acts as a ca sensor in IHCs for exocytosis and NT release 2) facilitates vesicle priming and replenishment 3) participates in exocytosis and endocytosis
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where is the conventional synapse?
in the CNS
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where is the ribbon synapse
in the mature IHC
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differences between ribbon synapses in cochlea and conventional?
1) IHC use otoferlin instead of synaptobrevin 1 and 2 2) all IHCs have synaptotagmin 4 3) diff type of ca subunits Cav1.2 (conventional), cav1.3 (ribbon)
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what is found in the hair cell and is present in conventional synapses but not all of them?
synaptotagmin 4
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what is the unique characterstic of Cav1.3?
it doesn't inactivate- it's important for continuous depolarisation
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what happens at a ribbon synapse when it gets depolarised?
depolarise the cell -> open ca channels -> ca channels influx form close coupling with vesicle called nanodomain as ca diffuses only a few nm away -> ca attaches to otoferlin -> causes vesicle release -> glutamate activates postynaptic -> auditory fi
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what does the mature ribbon synapse encode?
sustained and graded responses- can lead to 100 AP/sec in postsynaptic at synapses
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why can the auditory pathway be stimulated in both ways both excitatory and inhibitory
the MET channels always partially open so continually stimulating it, has a resting activity and this can be modulated, open MET channel more- depol- increase firing. Close MET channel- reduce it
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where has most of the work we know about the development of ribbon synapses been done?
in mice neurons
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why is mice neurons a good representation of what's ahppening in humans?
auditory system is very well conserved from a genetic and functional point of view, mice similar to humans and are mammalian as well
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when does the cells stop dividing and differentiate at the end of mitosis in mice?
early embryonic stages of development about E14.5
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when is the onset of hearing in mice?
Postnatal day 12
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can mice perceive sound when the cells are very mature at the terminal stage of mitosis/
no they need anther few weeks before the cochlea can hear sound
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when is the onset of hearing in humans?
5-6 months in utero
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what is happening before the onset of hearing when the cell and the cochlea do not get any sound information?
the cells mechanotransducer doesn't work because it's not stimulated by sound , they show spontaneous electrical activity = APs
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what is the difference between APs in neurons and spontaneous APs in the immature IHCs?
neurons- Na driven spontaneous immature - Ca driven
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what did we learn from the visual system?
early AP activity before the onset of sensory input are important for development- important for refining the auditory pathway
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what is different between the immature and mature ribbon synapse?
many more synpases in the immature than adult, ca channels are further away in immature = loose coupling in immature and tight coupling in mature
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what happens to RIBEYE in the mature and immature?
in immature its round becomes elongated in mature
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why is the machinery different in the immature vs mature?
has been been developed to encode 2 different receptor potentials
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when does the ribbon first appear?
in late embryonic stages
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what happens to shape of the ribbon in development?
its small and it grows and tends to be elevated and elongated in the adult
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why is this a simplistic representation?
the shape of the ribbon changes a lot depending on the frequency position but you can see theres always elongation change in shape in the adult ribbon
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what happens to the ca current in development?
ca current increases, decreases and becomes steady at this level in development
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what is very important in development and the onset of hearing?
ca coupling
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why does the ca current decrease and become study in development?
because you have a down-regulation of ca channels in development
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where are ca channels found in development?
only at the presynaptic side linked to the synaptic machinery
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in the mature cells where are they?
All over the cell as they're driving the ca AP so need a lot of ca to get this AP
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how does change in distibution change in dev?
ca channels are downregulated from the upper part of the cell and only concentrate at the bottom part of the cell
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how does the mature machinery look?
mature elongated ribbon and tightly coupled machinery
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immature machinery look like?
round, less tightly coupled machinery
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how did they prove this?
neurostaining confocal imaging of RIBEYE ribbon and glutamate
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where is glutamate localised?
2/3rds postsynaptic
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what colocalisation shows a functional synapse?
glutamate and RIBEYE
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where did glutamate and RIBEYE colocalise?
base of the cell, little at top = really tight coupling between them
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what was shown in the immature synapses?
many more RIBEYE posynaptic to support that there are many more connections
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in the immature synapse where are the ca channels?
not only present in the presynaptic and some don't colocalise with RIBEYE = dishomologous coupling
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what is the function of different organisation of synapses in mature and immature?
in mature everythings tightly coupled because of this when ca gets into the cell you generate a nanodomain coupling
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what is nanodomain coupling?
because they are tightly coupled (glutmate and ca channel) one ca that gets through the channel is enough to trigger the fusion of every single vesicle
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why is it called a nanodomain?
because ca only has to travel a few nm
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what do you get coupling between with the nanodomain?
coupling between ca channel and vesicle release (exocytosis)
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what is the signficance of having loose coupling in the immature?
Ca channels very far so ca will diffuse a few nm and won't reach the vescile so we have a microdomain, need the opening of several ca channels to create enough ca to diffuse and reach the vesicle
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how do you measure exocytosis (release of NT)?
capacitance = depolarise the cell, open ca channel, ca goes into cell and triggers vesicle fusion so vesicles are incorporated into the M so cell grows in size eg 10 vesicles CS will increase SA
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what is capacitance?
measure the change in cell surface to see how many vesicles are fusing, do capicitance measurements by giving a stimulus and seeing how many vesicles fuse into M
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why is there a linear relationship between the amount of ca channels and vesicle release?
one ca channel is sufficient to release one vesicle- linear relation its a function of the number of vesicles that fuse. 100 ca channels you have 100 vesicles so linear relation of NT
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why is it important to encode this graded rec potential?
need a linear relation to encode low to high sound intensities
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what is the function of having a nanodomain configuration and greater rec potential in the adult?
to encode different sound intensity
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what does having a large sound stimulus do?
large stimulus -> large ca current -> large NT release. this sensitivity might be for high to low so gives linearity same sensitivity throughout different sound intensities
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why do the small and high sound intensity have the same sensitivities?
because its a linear relationship between ca influx and vesicle release
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how is this different in the immature?
curve relation for one ca channel you get different numbers of NT release, lots of ca channels- why this relation is crucial for encoding APs
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why is the microdomain and loose coupling needed for a curved relationship?
have APs not sustained graded rec potentials - information is not encoded by sound intensity its encoded in specific timing- AP freuqency pattern so you need the timing of activity
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why don't you want NT release in between?
is not sustained you just want enough burst that will release enough NT to cause an AP, nothing then another burst, ruin timing if NT release in between, want the NT release at peak of AP peak Ca current
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Other cards in this set
Card 2
Front
what does sound do in mechanotransduction?
Back
displaces the sterociliary bundle, the displacement opens the MET channel and when they are open the K and also Ca go into the bundle but K generates receptor potential
Card 3
Front
why do we need to generate a receptor potential?
Back
Card 4
Front
why do you need to open ca channels?
Back
Card 5
Front
what needs to be encoded at the synapse for acoustic signals?
Back
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