Wow, I have been in this thread for a few days and it's like war here. *__*
I am really busy at the moment but I have seen so much misinformation around that it will be useful if I clear a few things out.
You guys seem to trip on the area I did not explain much because of its complexity (glutamate action and link).
I also saw some crazy theories about T. being permanent and irrevocable state. W T F people lol
I clear this area for once in the most simple way I can.
We all agree to that:
Noise trauma ==> Hair Cell death ==> glutamate release ==> Kv3.1 channel "lock"==> abnormal spontaneous firing ==> T.
So
what the fuck happen beteween glutamate release and the Kv channel abnomality, and why it's fucking reversible.
We all know that this bitch of glutamate is excitotoxic:
http://en.lmgtfy.com/?q=glutamate excitotoxicity
(CTRL+F, glutamate)
When the glutamate is released it forces the postsynaptic bouton to swell and burst.
(the pink thing is not a testicle)
View attachment 2703
"But but this Ca2+ is not glutamate, I don't understand, we will all die of T. !!"
Calm down son, increased extracellular glutamate levels leads to the activation of Ca2+ permeable NMDA receptors on myelin sheaths and oligodendrocytes, leaving oligodendrocytes susceptible to Ca2+ influxes and subsequent excitotoxicity.
(Boom )
View attachment 2704
"OMG OMG the postsynaptic bouton has exploded, my body is broken, we will all die of T. or maybe diarrhea!!"
No worries contrary to what was said above in the thread, we are the most complex mammal on earth because of our brain, and we are fully equiped to regenerate every fucking cell of our body, it's just not activated. Otherwise we would be Wolverines.
Which is not ok for me because I don't have a hairy chest...
View attachment 2705
Quite luckily the postsynaptic bouton is a little wolverine!!!
View attachment 2706
Step 1 it's normal, you just receive the acoustic trauma
Step 2 it fucking explode as mentionned above
Step 3 after 1 day it's reforming and the afferent dendrite has begun to grow upwards and some filopodia already reach the IHC. Wolvyyy powwaaa....Cochlear action potential begins to recover.
Step 4 the synaptic pattern is back on track and normal, well almost normal.
To rebuild any part of your body, exactly like for Ikea your body needs guidelines. And the plan of your body is in your genes.
View attachment 2707
However when the body reads the gene code to rebuild a part, it can be affected by external factors.
And this is here the glutamate comes into action to messs things up.
The over-expression of NMDA glutamate receptors change the structure of the dendrite, and synapse, because it wants to adapt to its new environement. We casually call that plasticity.
When the glutamate is gone (end of hair cell death), the dentrite and synapse stay locked in this particular way.
AM-101 try to avoid glutamate to provoke this "state" we casually call Tinnitus
"OMG OMG, so you see we have mutant dentrite creating never ending broken synapse, we will all die of T."
Calm down agaiiin!!! Morphogenesis and plasticity will save the day. This is the most flexible, evolutive, adaptive part of the body. Those fucking dentrites will readapt if we induce them in a new state and let plasticity consolidate it.
Unlike most neuro diseases, the error is not in your gene, your body knows what's the normal state.
So "in many cases, spine morphogenesis, plasticity, and maintenance also depend on synaptic activity", if you change this synaptic activity, give it enough time, and if it makes sense considering the initial physiological structure, then it will consolidate back again.
(More info on the phenomenon,
http://onlinelibrary.wiley.com/stor...38&s=ac1eb57600a4c22d4ab92eb463198f60a6bc3bea)
Conclusion, your brain is a little wolvy and knows what should be a normal state of connections (Kv & shit), it's just lock in a way becauce glutamate came to interfere with the natural reconstruction. If you force manually the right kv channel to work and let them consolidate, your brain will be like, "oh fuck this is the way, let's consolidate, yay".
End fo T.
(PS LoL: to the idiots who will think, if we destroy again the postsynaptic bouton without the glutmate it should be fine. NO NO NO it's a dumb idea you may kill the connection and there is high chance of no regeneration at all, meaning, hearing loss).
Peace