# Spontaneous Activity in Development of Auditory Processing Circuitry

> **NIH NIH F30** · JOHNS HOPKINS UNIVERSITY · 2020 · $50,520

## Abstract

Project Summary
 Developing auditory neurons assemble into rudimentary circuits that are subsequently modulated
through acoustic experience. Altered development of these circuits due to trauma, ototoxicity or congenital
deafness can lead to acoustic hypersensitivity, profound hearing loss, or debilitating tinnitus. Intrinsically
generated, “spontaneous” neural activity propagates through nascent auditory neural circuits prior to the onset
of acoustic input, providing an early training period that is thought to initiate key developmental processes.
However, the precise roles for spontaneous pre-hearing activity remain poorly understood. Our laboratory has
identified a critical role for inner supporting cells (ISCs) within the developing cochlea, which initiate a cascade
of events that trigger action potential firing in inner hair cells during the pre-hearing period. This process
critically depends upon opening of calcium-activated chloride channels (TMEM16A/ANO-1) that induce efflux
of K+ from ISCs. Genetic deletion of TMEM16A from ISCs dramatically reduces pre-hearing neural activity in
the auditory CNS in vivo, but TMEM16A cKO mice have preserved hearing thresholds and peripheral
responses to sound after ear canal opening, providing the means to interrogate how spontaneous activity
influences the maturation of central sound processing circuits via functional and behavioral assessments.
 Topographic organization is a defining feature of the sensory CNS. Pioneering experiments in the
visual system show that the sensory input an organism receives during restricted developmental periods is
critical for establishing, maintaining, and modulating precise topographic maps of the external world. Pre-
sensory neural activity is therefore likely critical for refining developmentally coarse topographic organization.
To assess if spontaneous pre-hearing activity in the developing auditory system contributes to refinement of
central tonotopic maps and neural tuning, I will dramatically reduce spontaneous activity in the auditory CNS
through deletion of TMEM16A within ISCs and subsequently image neural Ca2+ responses to sound in the
auditory midbrain and cortex just after hearing onset. I will determine if subsequent acoustic input is capable of
refining auditory cortical tonotopy without pre-hearing activity. Finally, I will identify if spontaneous activity
sharpens auditory circuitry and neural tuning required for tone discrimination through frequency-dependent
inhibition of the acoustic startle response and self-motivated operant conditioning behavioral paradigms.
 These experiments will provide important insight into how early acute injury to the cochlea and
congenital deafness lead to long-term changes in the capacity of auditory circuits to process and interpret
sounds, potentially leading to new approaches for improving auditory function in hearing impaired patients.

## Key facts

- **NIH application ID:** 10066095
- **Project number:** 1F30DC018711-01A1
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Calvin Jasper Kersbergen
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $50,520
- **Award type:** 1
- **Project period:** 2020-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10066095

## Citation

> US National Institutes of Health, RePORTER application 10066095, Spontaneous Activity in Development of Auditory Processing Circuitry (1F30DC018711-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10066095. Licensed CC0.

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