# Spontaneous activity in the developing auditory system

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2022 · $355,282

## Abstract

ABSTRACT
This application is in response to the Notice of Special Interest (NOT-AG-21-018) for Alzheimer's-focused
administrative supplements for NIH grants. Our currently funded parent R01 titled `Spontaneous activity in the
developing auditory system' does not currently focus on Alzheimer's disease (AD) or any of its related
dementias. We propose to leverage our unique expertise in studying neuron and astrocyte activity patterns in
the in vivo auditory system to extend Aims 2 and 3 of the parent R01 to determine how the progression of AD
relevant pathologies influence cellular activity patterns and transcriptional phenotypes in sound processing
centers. We will also determine if developmental disruptions in the stereotyped burst firing of neurons prior to
hearing onset influences the progression of AD pathogenesis. Hearing loss is a major risk factor for developing
dementias, including AD, and animal models of AD commonly develop auditory dysfunction at late stages of
disease, suggesting that manifestation of disease reflects an interplay between cellular activity in auditory
centers and AD progression, although the underlying mechanisms responsible for this link between hearing
and disease have not been determined. Sensory systems provide the added opportunity to define how disease
states alter neural processing in the intact brain. Notably, AD pathology is not limited to neurons. Astrocytes
adapt to changes in neural activity and respond to disease by changing their molecular and functional
properties (e.g. reactive astrogliosis), although how these phenotypic changes ultimately influence their
behavior in vivo, particularly in AD, is poorly understood. Given the crucial roles of astrocytes in ion and
neurotransmitter homeostasis, these reactive changes may profoundly impact local neural activity patterns and
exacerbate pathology. In this supplement, we will determine how spontaneous and sound-evoked activity of
both neurons and astrocytes is altered in the inferior colliculus and auditory cortex (two major processing
centers in the auditory pathway), from early development (prior to pathology) through the onset of gross
pathological changes (e.g., Aβ plaque formation). We will also determine how the transcriptional profiles of
both neurons and astrocytes change with the progression of AD pathology in the auditory system to better
define cell-type specific changes and identify potential therapeutic targets. Lastly, we will determine whether
disruptions in early activity in the auditory system influences disease progression later in life. These studies will
provide new insights into how AD influences network dynamics in the auditory system, and conversely how
altered cellular activity influences disease progression, which could reveal novel risk factors for AD and new
strategies for altering the trajectory of disease.

## Key facts

- **NIH application ID:** 10497913
- **Project number:** 3R01DC008860-10S1
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** DWIGHT E BERGLES
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $355,282
- **Award type:** 3
- **Project period:** 2007-12-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10497913

## Citation

> US National Institutes of Health, RePORTER application 10497913, Spontaneous activity in the developing auditory system (3R01DC008860-10S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10497913. Licensed CC0.

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