# Modulation of Exocytosis and Excitability in Mature Auditory Brainstem Neurons

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2022 · $375,943

## Abstract

PROJECT SUMMARY
The major goal of this Administrative Supplement is to determine the changes in neuronal excitability and
synaptic strength within the mammalian auditory brainstem during Alzheimer’s disease (AD) and during age
related hearing loss (ARHL). We will use well established transgenic mouse lines and strains as experimental
models for AD and ARHL. As proposed in our parent R01 grant, we will study two specialized synapses in the
auditory brainstem: the large calyx of Held synapse in the medial nucleus of the trapezoid body (MNTB) and the
small bouton-type glycinergic and glutamatergic synapses of the lateral superior olive (LSO). These synapses
are pivotal for the auditory brainstem circuits that compute high frequency sound source localization. Binaural
hearing constitutes an important mechanism for localizing sound sources in mammalian species. It also provides
a critical means for filtering important auditory inputs from background noise. The inability to distinguish sound
source location or perceive speech in noisy environments are common forms of hearing loss, especially in elderly
individuals. Impaired hearing also contributes for social isolation of individulas who suffer from ARHL, which
reduces their cognitive stimulation, aggravating or even leading to instances of dementia. The long-term goal is
to determine the neuronal excitability and biophysical properties of the MNTB and LSO synapses as animals
experience different stages of AD and ARHL progression. We will perform single cell patch clamp
electrophysiology recordings in mouse brainstem slices from adult and aging mice at different stages of
adulthood and aging in both control and AD models. Our preliminary data show that several fundamental aspects
of brainstem synapses and neuronal excitability are significantly changed already in young adult mice (three
month old) before severe symptoms of AD become clearly manifest. During adulthood and aging, further synaptic
and excitability changes are observed, sometimes in the opposite direction. We thus propose to study the
synaptic strength, short-term synaptic plasticity and neuronal excitability of neurons from the brains of AD and
ARHL mouse models. The first hypothesis is that the intrinsic excitability of LSO and MNTB neurons is
significantly reduced in AD and aging mice models making it harder for excitatory postsynaptic potentials
(EPSPs) to reach spike threshold. The second hypothesis is that the synaptic strength in AD and aging
brainstem synapses changes significantly because of changes in synaptic vesicle release probability and/or
changes in the readily releasable pool size of synaptic vesicles. The results will provide novel insights that reveal
several underlying mechanisms responsible for AD pathology and hearing deficits in young adults and aging
auditory neurons and synapses. The proposed studies will thus greatly stimulate additional activity leading to
significant progress on the fundamental causes of AD deme...

## Key facts

- **NIH application ID:** 10510150
- **Project number:** 3R01DC012938-07S1
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** HENRIQUE Prado VON GERSDORFF
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $375,943
- **Award type:** 3
- **Project period:** 2012-12-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10510150

## Citation

> US National Institutes of Health, RePORTER application 10510150, Modulation of Exocytosis and Excitability in Mature Auditory Brainstem Neurons (3R01DC012938-07S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10510150. Licensed CC0.

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