# Spontaneous activity in the developing auditory system

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2024 · $520,732

## Abstract

Project Summary
Neurons in the developing auditory system experience highly stereotyped bursts of activity prior to the onset of
sensory experience. This activity is initiated within the cochlea when non-sensory inner supporting cells
release ATP, triggering a cascade of events that ultimately induces trains of action potentials in spiral ganglion
neurons (SGNs) that propagate throughout the auditory system. The spatially restricted release of ATP triggers
correlated firing in groups of SGNs that will later encode similar frequencies of sound, providing a means to
induce activity-dependent maturation and refinement of sound processing circuits in the brain prior to hearing
onset. Despite the prominence of patterned activity during this critical developmental period, its role in
maturation of the auditory system remains poorly understood, in part, due to an inability to selectively disrupt
spontaneous activity while preserving sound transduction in the cochlea. Here, we propose to leverage newly
developed mouse models that allow selective disruption of spontaneous activity within cochlear supporting
cells yet preserve cochlear structure and the integrity of the auditory nerve. We will explicitly test the
hypothesis that burst firing of auditory neurons is critical to initiate structural and functional maturation of
nascent sound processing circuits. These studies will leverage genetic disruption of P2ry1 and Tmem16a, two
components required to generate spontaneous activity in cochlear supporting cells, with in vivo widefield and
two photon imaging of neuronal activity, RNA expression profiling and behavioral analyses of auditory function
to rigorously test this hypothesis. We will extend our recent discovery that astrocytes in the inferior colliculus
(IC) of pre-hearing mice are co-activated with surrounding neurons during spontaneous events, providing a
means to coordinate spatial and temporal maturation of tripartite synapses (excitatory synapses ensheathed by
astrocytes). Aim 1 will focus on the cochlea, determining how loss of P2RY1 and TMEM16A influence the
properties and developmental trajectory of SGNs. Aim 2 will define the relationship between cochlear and
extra-cochlear spontaneous activity in auditory cortex (AC), determine how disruption of cochlea-derived
spontaneous activity alters spatial patterns of neuronal activation in the IC and AC and ultimately influence
auditory discrimination. Aim 3 will define the patterns of neuronal activity required to induce calcium elevation
in astrocytes and determine how selective genetic disruption of astrocyte mGluR5 expression, which is
necessary to detect neuronal burst firing, influences astrocyte maturation and progressive refinement of
tonotopic representation of sounds in vivo. These studies will provide greater insight into the fundamental
mechanisms used to define circuits that process sound information and establish a framework to explore how
genetic mutations, trauma and exposure to otot...

## Key facts

- **NIH application ID:** 10836423
- **Project number:** 5R01DC008860-12
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** DWIGHT E BERGLES
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $520,732
- **Award type:** 5
- **Project period:** 2007-12-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10836423

## Citation

> US National Institutes of Health, RePORTER application 10836423, Spontaneous activity in the developing auditory system (5R01DC008860-12). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10836423. Licensed CC0.

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