# Synaptic mechanisms of auditory information processing

> **NIH NIH R01** · TULANE UNIVERSITY OF LOUISIANA · 2021 · $323,000

## Abstract

PROJECT SUMMARY
The reliability and precision of synaptic transmission are required in circuits of the auditory brainstem in order to
encode timing with submillisecond accuracy. Auditory information is encoded by action potentials phase-locked
to sound frequency at high rates. Accordingly, synaptic vesicles need to be recycled and refilled rapidly.
Accumulating studies have uncovered the processes of vesicle fusion and recycling; however, the control of the
contents of synaptic vesicles has received considerably less attention. Reasons for this gap in our understanding
include the small size of synaptic vesicles and of conventional synapses, the complex ionic basis for loading of
neurotransmitter into vesicles, and the difficulty in manipulating and assessing vesicle loading in physiological
conditions. We have recently found that a Na+/H+ exchanger expressed on synaptic vesicles promotes vesicle
filling with glutamate. Using the calyx of Held, a giant glutamatergic synapse in the auditory brainstem that
permits direct pre- and postsynaptic recordings and manipulation of the presynaptic cytosol, we showed that
glutamate loading is facilitated by intracellular Na+ over the physiological concentration range. Na+ influx through
presynaptic plasma membrane HCN channels affects presynaptic Na+ concentration, regulates glutamate uptake,
and thus controls miniature excitatory postsynaptic currents. Here we propose that during high-frequency
signaling, when large amounts of glutamate are released, Na+ accumulates in terminals and facilitates glutamate
uptake into synaptic vesicle, accelerating vesicle replenishment and sustaining reliable synaptic transmission.
We further hypothesize that the control of vesicle loading, release and recycling can be affected by hearing loss.
This work will establish a new fundamental role of Na+ to link activity and synaptic function under physiological
and pathological conditions.

## Key facts

- **NIH application ID:** 10132290
- **Project number:** 5R01DC016324-04
- **Recipient organization:** TULANE UNIVERSITY OF LOUISIANA
- **Principal Investigator:** Hai Huang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $323,000
- **Award type:** 5
- **Project period:** 2018-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10132290

## Citation

> US National Institutes of Health, RePORTER application 10132290, Synaptic mechanisms of auditory information processing (5R01DC016324-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10132290. Licensed CC0.

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