Background

Stress-related auditory complaints—particularly tinnitus, sound intolerance, and fluctuating hearing symptoms—are frequently reported in clinical practice. While central auditory and limbic mechanisms of stress have been extensively studied, the auditory periphery has long been considered a passive recipient of stress-related modulation. Emerging evidence challenges this assumption.

Acute activation of the hypothalamic–pituitary–adrenal (HPA) axis leads to rapid release of glucocorticoids, which are known to induce synaptic remodeling in the central nervous system. However, whether similar mechanisms operate at the inner hair cell–spiral ganglion neuron synapse, the first synapse of the auditory pathway, has remained largely unexplored. Moreover, sex-dependent differences in stress responsiveness are increasingly recognized across neuroscience, yet are rarely addressed in auditory research.

Recent experimental work demonstrates that stress hormones directly modulate synaptic architecture in the cochlea, revealing sex-specific patterns of plasticity mediated by glucocorticoid receptors. These findings provide a novel mechanistic framework linking stress physiology with peripheral auditory dysfunction.

Description

This keynote lecture will present and contextualize new experimental evidence demonstrating that acute exposure to stress hormones induces rapid, sex-dependent synaptic remodeling at the inner hair cell synapse. Using organotypic cochlear models, the lecture will illustrate how corticosterone alters presynaptic ribbon size, postsynaptic AMPA receptor organization, and synaptic colocalization without causing overt cellular damage.

The talk will integrate molecular, synaptic, and functional perspectives, bridging basic auditory neuroscience with clinically relevant phenomena, including tinnitus, hyperacusis, and stress-related hearing fluctuations. Particular emphasis will be placed on sex as a biological variable, receptor-specific mechanisms, and the concept of the cochlea as a stress-responsive organ.

The lecture will conclude by discussing translational implications for individualized auditory care and future research directions in stress-related otology

Outcome Objectives

After attending this keynote lecture, participants will be able to:

1.     Recognize the auditory periphery as an active target of stress hormones, rather than a purely mechanically driven system.

2.     Understand sex-dependent mechanisms of synaptic plasticity at the inner hair cell–spiral ganglion neuron synapse.

3.     Explain the role of glucocorticoid receptors in cochlear synaptic remodeling under acute stress conditions.

4.     Integrate stress biology into clinical reasoning for tinnitus and other stress-associated auditory disorders.

5.       Identify emerging translational opportunities for sex-sensitive and stress-informed approaches in otology and audiology.

Background

The inner ear has long been considered an immune-privileged organ. However, accumulating evidence demonstrates that the healthy mammalian inner ear contains a resident population of immune cells, including macrophages, lymphocytes, leukocytes, and mast cells, distributed across cochlear and vestibular structures. A recent scoping review systematically summarized more than four decades of experimental and human data, revealing the consistent presence of immune cells in the stria vascularis, spiral ligament, spiral ganglion, organ of Corti, and endolymphatic sac under steady-state conditions.

Despite this growing body of evidence, the physiological roles of these resident immune cells remain poorly understood, and their contributions to inner-ear homeostasis and pathology are underrepresented in clinical education. This knowledge gap limits progress in understanding inflammatory, autoimmune, and degenerative auditory disorders.

Course Description

This instructional course will provide a structured introduction to inner ear immunology under physiological conditions, based on a comprehensive synthesis of animal and human data. Participants will learn which immune cell types reside in the inner ear, how they are identified, and where they are localized across species.

The course will cover:

•            The historical concept of immune privilege versus current evidence of immune residency

•            Immune cell types present in the mammalian inner ear and their anatomical distribution

•            Differences and similarities between rodent and human inner ear immune landscapes

•            Methodological approaches used to study immune cells in cochlear tissue

•            Emerging hypotheses on immune-mediated homeostasis, repair, and pathology

Clinical correlations will include autoimmune inner ear disease, noise-induced hearing loss, cochlear implantation, and age-related auditory decline. Emphasis will be placed on integrating immunological concepts into otologic thinking rather than on immunotherapy per se.

Learning Objectives / Outcomes

After completing this course, participants will be able to:

1.           Describe the types of immune cells residing in the mammalian inner ear under steady-state conditions.

2.           Identify key cochlear and vestibular structures involved in inner ear immune surveillance.

3.           Understand experimental and histological methods used to study immune cells in the inner ear.

4.           Recognize the potential roles of resident immune cells in auditory homeostasis and disease.

5.           Integrate inner ear immunology into clinical reasoning for inflammatory and immune-mediated auditory disorders.