Exposure to non-traumatic noise in vivo drives long-lasting changes in auditory nerve synapses, which may influence hearing, but the induction mechanisms are not known. We mimicked activity in acute slices of the cochlear nucleus from mice of both sexes by treating them with high potassium, after which, voltage-clamp recordings from bushy cells indicated that auditory nerve synapses had reduced EPSC amplitude, quantal size, and vesicle release probability (P r). The effects of high potassium were prevented by blockers of nitric oxide (NO) synthase and protein kinase A. Treatment with the NO donor, PAPA-NONOate, also decreased P r, suggesting NO plays a central role in inducing synaptic changes. To identify the source of NO, we activated auditory nerve fibers specifically using optogenetics. Strobing for 2 hr led to decreased EPSC amplitude and P r, which was prevented by antagonists against ionotropic glutamate receptors and NO synthase. This suggests that the activation of AMPA and NMDA receptors in postsynaptic targets of auditory nerve fibers drives release of NO, which acts retrogradely to cause long-term changes in synaptic function in auditory nerve synapses. This may provide insight into preventing or treating disorders caused by noise exposure.SIGNIFICANCE STATEMENTAuditory nerve fibers undergo long-lasting changes in synaptic properties in response to noise exposure in vivo, which may contribute to changes in hearing. Here we investigated the cellular mechanisms underlying induction of synaptic changes using high potassium and optogenetic stimulation in vitro, and identified important signalling pathways using pharmacology. Our results suggest that auditory nerve activity drives postsynaptic depolarization through AMPA and NMDA receptors, leading to the release of nitric oxide, which acts retrogradely to regulate presynaptic neurotransmitter release. These experiments revealed that auditory nerve synapses are unexpectedly sensitive to activity, and can show dramatic, long-lasting changes in a few hours that could affect hearing.
Pharmacology, Toxicology and Pharmaceutical Science
1
10%
Agricultural and Biological Sciences
1
10%
Unknown
6
60%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 6. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 18 August 2022.
All research outputs
#9,530,893
of 34,386,255 outputs
Outputs from Journal of Neuroscience
#10,431
of 23,398 outputs
Outputs of similar age
#124,377
of 463,851 outputs
Outputs of similar age from Journal of Neuroscience
#86
of 181 outputs
Altmetric has tracked 34,386,255 research outputs across all sources so far. This one has received more attention than most of these and is in the 72nd percentile.
So far Altmetric has tracked 23,398 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 15.3. This one has gotten more attention than average, scoring higher than 55% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 463,851 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 73% of its contemporaries.
We're also able to compare this research output to 181 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 52% of its contemporaries.
