NIH grant: Auditory-Arousal Circuits in Normal and Disordered Hearing (1R01DC023339-01A1)

retained text

NIH grant 1R01DC023339-01A1: Auditory-Arousal Circuits in Normal and Disordered Hearing
Institute: {'code': 'DC', 'abbreviation': 'NIDCD', 'name': 'National Institute on Deafness and Other Communication Disorders', 'admin_org_id': '12500019', 'admin_funding_url': ''}. PI: Anna R Chambers. Award: $467323.
Start: 2026-07-10T00:00:00.
Unlike other sensory modalities, the auditory system maintains its sensitivity at all times, modulating vigilance across
brain states, from active wakefulness to deep sleep. Through their widespread connectivity with arousal centers, auditory
circuits can rapidly and potently mobilize us to act on potential threats, making sound perception inextricable from
arousal state. However, most of what we know about auditory encoding and perception comes from experiments
performed in awake subjects, particularly in the case of hearing loss and hearing perceptual disorders. Meanwhile,
sleep disruption is one of the primary complaints of patients with hearing disorders such as tinnitus, and is common
among people with sensorineural hearing loss. Decades of research on the consequences of hearing loss for the brain
point to a possible mechanism—central auditory hyperactivity. Following the loss of peripheral inputs, central circuits
compensate by increasing spontaneous activity, synchrony, and sound response gain. Our core hypothesis is that after
hearing loss, hyperactive auditory neurons more readily recruit arousal via auditory-arousal circuits in the brain, where
sound information is relayed to neurons that wake us rapidly and robustly from sleep. For the first time, central
auditory function will be characterized across all brain states, including sleep, and arousal dysregulation will be related
to the degree of auditory perceptual gain measured with a behavioral task. Sleep quality and quantity, including markers of
sleep- related cognition, before and after hearing loss, will be systematically studied in the noise-induced hearing loss
(NIHL) model, which produces a permanent threshold shift at high sound frequencies while leaving lower frequency
hearing intact. This profile of steeply sloping high frequency hearing loss is common in the human population and is
associated with tinnitus. Aim 1 of this project seeks to characterize a comprehensive sleep/wake profile of a
mouse model of NIHL using freely moving electrophysiology and quantitative videography. A loudness categorization
task will enable us to relate the degree of auditory perceptual gain to the degree of arousal dysregulation, motivating the
usage of objective sleep metrics as potential biomarkers and outcome measures for the diagnosis and treatment of
hearing perceptual disorders such as hyperacusis and tinnitus. Preliminary data shows that after NIHL, mice exhibit
significantly fragmented non-rapid eye movement (NREM) sleep and wake more readily to moderate intensity sounds.
Aims 2 and 3 are based on the hypothesis that auditory circuit hyperactivity is to blame, and uses a combination of viral-
genetic circuit dissection methods, optogenetics and chronic single-unit recordings available in mice to investigate the
auditory-arousal circuitry where NIHL-induced hyperactivity and increased sound response gain may recruit wake-
promoting neurons. Given the rising prevalence hearing loss, dementia and insomnia among the world’s population, it
is the long- term objective of this project to investigate the interconnected causes and consequences of these disorders in
a mouse model with measures that are readily translatable to parallel human patient studies.

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