From hidden hearing loss to supranormal auditory processing by neurotrophin 3-mediated modulation of inner hair cell synapse density

Loss of synapses between spiral ganglion neurons and inner hair cells (IHC synaptopathy), leads to an auditory neuropathy called hidden hearing loss (HHL) characterized by normal auditory thresholds but reduced amplitude of sound-evoked auditory potentials. It has been proposed that synaptopathy and HHL result in poor performance in challenging hearing tasks despite a normal audiogram. However, this has only been tested in animals after exposure to noise or ototoxic drugs, which can cause deficits beyond synaptopathy. Furthermore, the impact of supernumerary synapses on auditory processing has not been evaluated. Here, we studied mice in which IHC synapse counts were increased or decreased by altering neurotrophin 3 (Ntf3) expression in IHC-supporting cells. As we previously showed, postnatal Ntf3 knockdown or overexpression reduces or increases, respectively, IHC synapse density and suprathreshold amplitude of sound-evoked auditory potentials without changing cochlear thresholds. We no..., Animals: All experimental procedures complied with the National Institutes of Health guidelines and were approved by the Institutional Animal Care and Use Committee of the University of Michigan, MI, USA. Cochlear supporting-cell specific Ntf3 knock-down mice (Ntf3 KD) derived from Ntf3flox/flox:Plp1/CreERT mice by Cre-recombination) and Ntf3 overexpressing mice (Ntf3 OE derived from Ntf3stop:Plp1/CreERT mice by Cre-recombination) were generated. Ntf3 KD mice and their controls were maintained on C57BL/6 background. Ntf3 OE and their controls were on FVB/N background. Both male and female mice were included in this study.
Tamoxifen administration: Tamoxifen was injected into the intraperitoneal cavity of P 3-10 Ntf3stop: Plp1/CreERT mice or P1-3 Ntf3flox/flox:Plp1/CreERT mice. A 10 mg/ml solution of tamoxifen was obtained by dissolution in corn oil. Injection was 33 mg/kg for Ntf3stop: Plp1/CreERT mice and 50 mg/kg for Ntf3flox/flox:Plp1/CreERT mice.
Real-time quantitative RT-PCR: Total..., Excel, imageJ, EPL ABR analysis software, # From hidden hearing loss to supranormal auditory processing by neurotrophin 3-mediated modulation of inner hair cell synapse density

This IHC_2024__DATA_README.doc file was generated on 2024-04-01 by Lingchao Ji

#### GENERAL INFORMATION

1. Title of Dataset: Data from: From Hidden Hearing Loss to Supranormal Auditory Processing by Neurotrophin 3-mediated Modulation of Inner Hair Cell Synapse Density.
2. Author Information

Corresponding Investigator
Name: Dr Gabriel Corfas
Institution: Kresge Hearing Research Institute and Dept. of Otolaryngology, University of Michigan, USA
Email: [[e-mail]](mailto:[e-mail])

Co-investigator 1
Name: Dr Lingchao Ji
Institution: Kresge Hearing Research Institute and Dept. of Otolaryngology, University of Michigan, USA

Co-investigator 2
Name: Dr Beatriz C. Borges
Institution: Kresge Hearing Research Institute and Dept. of Otolaryngology, University of Michigan, USA

Co-investigator 3
Name: Dr David T. Martel
Institution: Kre...