Related Experiment Video
Updated: Nov 15, 2025
Morphological and Functional Evaluation of Ribbon Synapses at Specific Frequency Regions of the Mouse Cochlea
Published on: May 10, 2019
Effects of combined gentamicin and furosemide treatment on cochlear ribbon synapses
Liana Sargsyan1, Alisa P Hetrick1, Jessica G Gonzalez1
1Research Service, VA Loma Linda Healthcare System, CA 92357, USA.
Abstract:
It is well-established that aminoglycoside antibiotics are ototoxic, and the toxicity can be drastically enhanced by the addition of loop diuretics, resulting in rapid irreversible hair cell damage. Using both electrophysiologic and morphological approaches, we investigated whether this combined treatment affected the cochlea at the region of ribbon synapses, consequently resulting in auditory synaptopathy. A series of varied gentamicin and furosemide doses were applied to C57BL/6 mice, and auditory brainstem responses (ABR) and distortion product otoacoustic emissions (DPOAE) were measured to assess ototoxic damage within the cochlea. In brief, the treatment effectively induced cochlear damage and promoted a certain reorganization of synaptic ribbons, while a reduction of ribbon density only occurred after a substantial loss of outer hair cells. In addition, both the ABR wave I amplitude and the ribbon density were elevated in low-dose treatment conditions, but a correlation between the two events was not significant for individual cochleae. In sum, combined gentamicin and furosemide treatment, at titrated doses below those that produce hair cell damage, typically triggers synaptic plasticity rather than a permanent synaptic loss.
Insights
Combined gentamicin and furosemide treatments, at low doses, promote synaptic plasticity in the cochlea. This indicates potential for auditory synaptopathy without significant hair cell damage.
Area of Science:
- Ototoxicology
- Neuroscience
- Auditory Science
Background:
- Aminoglycoside antibiotics and loop diuretics are known ototoxic agents.
- Their combined use can lead to rapid, irreversible hair cell damage.
- The impact on cochlear ribbon synapses and auditory synaptopathy is not fully understood.
Purpose of the Study:
- To investigate the effects of combined gentamicin and furosemide treatment on cochlear ribbon synapses.
- To determine if this combination induces auditory synaptopathy.
- To assess the relationship between synaptic changes and hair cell damage.
Main Methods:
- C57BL/6 mice were treated with varied doses of gentamicin and furosemide.
- Auditory brainstem responses (ABR) and distortion product otoacoustic emissions (DPOAE) were measured.
- Electrophysiologic and morphological analyses were employed to assess cochlear and synaptic integrity.
Main Results:
- Combined treatment induced cochlear damage and synaptic ribbon reorganization.
- Significant reduction in ribbon density was observed only after substantial outer hair cell loss.
- Low-dose treatment elevated ABR wave I amplitude and ribbon density, but without significant correlation.
Conclusions:
- Combined gentamicin and furosemide treatment at doses below those causing hair cell damage primarily induces synaptic plasticity.
- This suggests a potential for reversible changes at the auditory nerve synapse.
- The findings differentiate between synaptic plasticity and permanent synaptic loss in ototoxicity.
More Related Videos
12:21The Mouse Round-window Approach for Ototoxic Agent Delivery: A Rapid and Reliable Technique for Inducing Cochlear Cell Degeneration
Published on: November 26, 2015
09:06Cochlear Implant Surgery and Electrically-evoked Auditory Brainstem Response Recordings in C57BL/6 Mice
Published on: January 9, 2019
