Exam 1 (Tinnitus Mechanisms) Flashcards
Challenges to Understanding Mechanisms of Tinnitus
Assessment limitations
Limitations of animal mode
Complexity of the auditory system
hard to understand what causes a person to perceive it because there is difficulty in accurately diagnosing tinnitus in humans (no objective tests to show there actually is tinnitus), in animals you can look at so many things but a limitation because they cannot talk they don’t know, and lastly we know auditory system is complex and redundant (ipsi and contra and certain lesions have a greater impact on things than others etc)
Theories of peripheral mechanisms
cellular mechanisms
edge theory
discordant damage of IHC and OHCs
tectorial membrane displacement
NTs and their receptors
synaptopathy
describe cellular mechanisms of Theories of peripheral mechanisms:
cochlear damage can involve
Loss of OHC electromotility - cochlear amplifiers, affect our sensory ability to hear really soft sounds
Loss of synapses between IHCs and spiral ganglion neurons (synaptopathy) -
Damage to the stereociliary bundle
Rupture of the basilar membrane - affects everything, fluid can mix (toxic)
Death of OHCs or IHCs
aka contrast theory
edge theory
what is the edge theory
Tinnitus is induced by increased spontaneous activity in the edge area
what is the edge area in the edge theory
Area representing a transition from normal OHCs on the apical side of a lesion to OHCs toward the basal side that are missing or altered
Region between the damage and healthy area of increased spontaneous activity
Area of transition: more IHCs are functional and OHC is the damage so the extra work done by the IHC is hyperactivity
true
describe discordant damage of iHC or OHCs of Theories of peripheral mechanisms:
noise & ototoxicity leads to imbalance of stereocilia damage (IHC & OHC loss), which causes nerve fiber imbalance (type I and II) causing altered higher brain centers that leads to tinnitus
if there is noise or ototoxicity, it can lead to cochlear damage, which can cause HL in HFs (4-6 kHz) and this suggests leading to an imbalance of IHC & OHCs (IHCs are more resilient to damage than OHCs - in areas of max damage both are damaged and those with less damaged there will be damaged OHCs but healthy IHCs)
end result is that the imbalance is carried out to the brain so it is perceived as tinnitus
limitations to the discordant damage of iHC & OHCs
it is based on the imbalance between healthy and unhealthy structure making it not uniform and leading to hyperactivity
Profound HL - means there is max damage of loss & if it is a uniform loss then there shouldn’t be any increased activity
what happens to damage of OHCs in the two fundamental processes of the OHC
Intracellular calcium levels
Biochemical changes in the structural proteins of OHCs
messenger, helps to transmit impulses between the nerve and cells
NT
excitatory NT
glutamate
inhibitory NT
GABA
what are examples of nTs in the AS
Glutamate (excitatory) and GABA (inhibitory)
what mediates the NTs in the auditory system (glutamate & GABA)
AMPA - (Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid)
NMDA (N-methyl-D-aspartate)
what leads to tinnitus in NT & receptors
When this balance is messed up between excitatory and inhibitory, leads to spontaneous activity; how NT bind to AMPA & NMDA leads to spontaneous activity
Tectorial membrane displacement for theories of peripheral mechanisms
there is hyperactivity but is related to detachment of ™ causing sagging causing IHC to depolarize and this chronic depolarization is hyperactivity heard by the brain
Tectorial membrane position changes can trigger acute tinnitus following intense noise exposure and can result from
Tectorial membrane detachment
Shouldn’t normally touch the IHCs but when detachment occurs it causes it to sag over them and depolarize them
This leads to depolarization, then hyperactivity and then is heard as tinnitus by the brain
Tectorial membrane position changes can trigger acute tinnitus following intense noise exposure and can result from
tectorial membrane detachment
increased pressure in the scala media
degeneration of oHCs or stereocilia
NT & receptors in peripheral mechanism of tinnitus
Since there is overstimulation there is a massive amount of glutamate not usually produced
When calcium channels open at the bottom, calcium channels dump more in the cell than normal
Calcium comes from perilyphm that is rich in this
This causes glutamate to dump more than the normal amount at the synaptic cleft causing it to accumulate and overwhelm the reuptake mechanisms (doesn’t clear as fast as normal) causing it to stay at the cleft and leads to overstimulation of the receptors
hair cells stimulate, releases excess glutamate that the cell doesn’t usually need resulting in excess calcium to stay at the synaptic cleft and over stimulates the receptors which damages the level of the nerve fibers as well as damage inside the hair cells resulting in nerve loss and hair cell loss through apoptosis
what would an increase in glutamate do in AMPA receptors?
Damage (noise exposure), causes excessive glutamate released by the IHCs leading to overactiviation of the AMPA receptor, this results in excessive calcium influx (more than normal and too much causes nerve cell damage - makes an enzyme that kills the cell) and in turn disrupts the auditory signal that goes to the brain resulting in the perception of tinnitus
what would an increase in glutamate do in NMDA receptors
There is damage, glutamate is overstimulated causing overactivation at the NMDA receptor, leads to excessive calcium influx, which disrupts the neural activity, this leads to an enhanced spontaneous firing and hyperactivity of the auditory nerve leading to tinnitus perception
synaptopathy
involves damage specifically to the synapses without necessarily affecting the hair cells or causing immediate, measurable hearing loss on standard audiograms.
hidden hearing loss
what is HHL
irreversible damage to synapses between iHCs and the cochlear nerve fibers - causes tinnitus, hyperacusis & issues hearing in noise
f
Noise induced excitotoxicity causes excessive glutamate release from IHC synapses leading to
swelling of dendrite, partial disconnection of IHCs from afferent neurons and results in hearing loss and tinnitus