# Preservation of timing in plastic auditory pathways

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2020 · $408,186

## Abstract

PROJECT SUMMARY
 The hair cell synapse is the first step in the ascending auditory pathway. Disruption of this ribbon-type
synapse can lead to severe hearing disorders. The goal of this proposal is to investigate how hair cell synaptic
activity provides rapid signaling for long periods of time without fatigue. To maintain a continuous release of
neurotransmitter the hair cell requires a large pool of synaptic vesicles that are readily releasable. However,
the mechanisms that regulate synaptic vesicle endocytosis and the replenishment of vesicle pools in hair cells
are poorly understood. We propose here to study fundamental aspects of synaptic transmission at inner hair
cells (IHCs) in mouse cochlea and at auditory hair cells in the adult bullfrog amphibian papilla (AP). The AP
preparation allows us to routinely access single hair cells and their afferent fibers for high-time-resolution
patch-clamp electrophysiology and structure/function studies. We propose to use paired recordings of the hair
cell and its connected afferent fiber to study multivesicular release and simultaneously to measure membrane
capacitance changes from the hair cell to assay the exocytosis and endocytosis of synaptic vesicles. We will
pursue three Specific Aims: First, we hypothesize that the fast and phasic component of release from hair cells
requires high levels of ATP synthesis and hydrolysis, whereas the sustained component of release persists at
a reduced rate even when ATP levels are very low. Accordingly, hair cells contain numerous mitochondria that
are located near synaptic ribbons suggesting a need for a large amount of local ATP. Second, we will test the
role of internal pH in controlling the rate of endocytosis in hair cells. Finally, we will study a transient block of
the Ca2+ current in post-hearing mouse IHCs that is caused by the release of protons during multivesicular
exocytosis. This transient block of the Ca2+ current constitutes a new method to study multivesicular release at
IHC synapses and a new mechanism to explain the rapid spike adaption that is observed in vivo at the
mammalian auditory nerve. Together these experiments will determine how pH changes affect endocytosis at
hair cells and they will clarify the contributions of metabolic mechanisms that influence the auditory hair cell's
ability to continuously release neurotransmitter.

## Key facts

- **NIH application ID:** 9850563
- **Project number:** 5R01DC004274-20
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** HENRIQUE Prado VON GERSDORFF
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $408,186
- **Award type:** 5
- **Project period:** 2000-03-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9850563

## Citation

> US National Institutes of Health, RePORTER application 9850563, Preservation of timing in plastic auditory pathways (5R01DC004274-20). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9850563. Licensed CC0.

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