MemberNoise Trauma-Induced Behavioral Gap Detection Deficits Correlate with Reorganization of Excitatory and Inhibitory Local Circuits in the Inferior Colliculus and Are Prevented by Acoustic Enrichment
Joshua J. Sturm, Ying-Xin Zhang-Hooks, Hannah Roos, Tuan Nguyen and Karl Kandler
Journal of Neuroscience 28 June 2017, 37 (26) 6314-6330; DOI: https://doi.org/10.1523/JNEUROSCI.0602-17.2017
Apologies if this study has already been discussed, but I think it makes some very important points that are worth considering.
The authors induced acoustic trauma in juvenile mice with exposure to intense noise. About a week later they assessed the level of cochlear damage and auditory nerve damage and also tested the mice in a simple (often maligned) behavior that can reveal an auditory processing problem consistent with tinnitus. They found that about half of their mice showed behavioral effects consistent with tinnitus even though their cochlear damage was exactly matched. So what explains the behavioral manifestation of tinnitus or no tinnitus? To answer this question, they made recordings from single neurons in a midbrain structure called the inferior colliculus (as has been done many many times). The new innovation here is that they didn't treat every neuron in the inferior colliculus as being the same. Because they aren't!. Some neurons are inhibitory (they inhibit downstream neurons) whereas other neurons are excitatory (they activate downstream neurons). The authors discovered that mice with abnormal behavior consistent with tinnitus show a "signature" of imbalance between the inhibitory and excitatory circuits that were not observed in mice with equally matched cochlear damage that do not show signs of tinnitus. The authors drill down the synaptic inputs onto excitatory and inhibitory neurons and show a complementary set of changes wherein the excitatory and inhibitory synaptic inputs change in opposite ways when recording from neurons that activate versus inhibit other neurons. The inhibition was reduced while the excitation was enhanced in a cell type-specific manner which summed up to create a hyper-excitable brain only in the noise-damaged mice that showed tinnitus.
This is an important discovery because it is among the first to relate synaptic changes to a behavior that is related to tinnitus and - more importantly - to break the findings down between fundamentally different kinds of cells in the brain. Had they not done this (in other words, had they just treated every neuron as being the same as the next) the effect they described would have canceled each other out and they wouldn't have seen much. Sadly, most every study performed in intact brains has been unable to make this leap, which has greatly hampered progress understanding the neural sources of tinnitus.
They did a final set of experiments wherein mice with cochlear damage were passively exposed to moderately loud pulsed white noise (imagine the sound of the rotary blades of a helicopter) shortly after the damage. They found that the incidence of behavioral and neurophysiological changes consistent with tinnitus were much lower in this sound-exposed group, suggesting an early window of intervention following noise exposure that could forestall the pathology that ultimately may lead to tinnitus.
There are a bunch of caveats and issues with this study (as with any study) but I have gone on long enough so I can address that later if anyone cares.
Joshua J. Sturm, Ying-Xin Zhang-Hooks, Hannah Roos, Tuan Nguyen and Karl Kandler
Journal of Neuroscience 28 June 2017, 37 (26) 6314-6330; DOI: https://doi.org/10.1523/JNEUROSCI.0602-17.2017
Apologies if this study has already been discussed, but I think it makes some very important points that are worth considering.
The authors induced acoustic trauma in juvenile mice with exposure to intense noise. About a week later they assessed the level of cochlear damage and auditory nerve damage and also tested the mice in a simple (often maligned) behavior that can reveal an auditory processing problem consistent with tinnitus. They found that about half of their mice showed behavioral effects consistent with tinnitus even though their cochlear damage was exactly matched. So what explains the behavioral manifestation of tinnitus or no tinnitus? To answer this question, they made recordings from single neurons in a midbrain structure called the inferior colliculus (as has been done many many times). The new innovation here is that they didn't treat every neuron in the inferior colliculus as being the same. Because they aren't!. Some neurons are inhibitory (they inhibit downstream neurons) whereas other neurons are excitatory (they activate downstream neurons). The authors discovered that mice with abnormal behavior consistent with tinnitus show a "signature" of imbalance between the inhibitory and excitatory circuits that were not observed in mice with equally matched cochlear damage that do not show signs of tinnitus. The authors drill down the synaptic inputs onto excitatory and inhibitory neurons and show a complementary set of changes wherein the excitatory and inhibitory synaptic inputs change in opposite ways when recording from neurons that activate versus inhibit other neurons. The inhibition was reduced while the excitation was enhanced in a cell type-specific manner which summed up to create a hyper-excitable brain only in the noise-damaged mice that showed tinnitus.
This is an important discovery because it is among the first to relate synaptic changes to a behavior that is related to tinnitus and - more importantly - to break the findings down between fundamentally different kinds of cells in the brain. Had they not done this (in other words, had they just treated every neuron as being the same as the next) the effect they described would have canceled each other out and they wouldn't have seen much. Sadly, most every study performed in intact brains has been unable to make this leap, which has greatly hampered progress understanding the neural sources of tinnitus.
They did a final set of experiments wherein mice with cochlear damage were passively exposed to moderately loud pulsed white noise (imagine the sound of the rotary blades of a helicopter) shortly after the damage. They found that the incidence of behavioral and neurophysiological changes consistent with tinnitus were much lower in this sound-exposed group, suggesting an early window of intervention following noise exposure that could forestall the pathology that ultimately may lead to tinnitus.
There are a bunch of caveats and issues with this study (as with any study) but I have gone on long enough so I can address that later if anyone cares.
