Noise-induced, drug-induced, and congenital hearing loss results from damage to hair cells, the sensory receptors of the inner ear. With half of Americans over 75 afflicted by moderate to severe hearing impairment and a worldwide rise in the prevalence of hearing impairment in younger adults, hearing loss is a significant public-health concern. Knowledge of the normal operation of the hair cell-including that of its mechanical antenna, the hair bundle-will contribute to understanding the pathophysiology of hearing loss and developing treatments for it. The proposed study seeks to examine the dynamical properties of a hair bundle that underlie its ability to amplify mechanical stimuli. As a dynamical system, the activity of a hair bundle can be characterized by a state space that describes the bundle's behavior under various conditions. Included in the state space is a Hopf bifurcation, an instability that endows the hair bundle with the ability to self-tune near criticalty. This dynamical system can be readily explored by manipulation of two control parameters, offset force and stiffness. I will attempt to coerce the hair bundle to cross its critical point, demonstrating for the first time the presence of a Hopf bifurcation embedded in hair-bundle mechanics. This demonstration will provide a tool for further investigation of phenomena characteristic of the active process in hearing. Thus, by controlling mechanical properties, I shal elucidate the functions of hair bundles that endow humans with highly resolved auditory sensation.

Public Health Relevance

Over 10% of Americans are affected by hearing impairment, and characterizing the means by which normal hearing functions at a high fidelity will contribute to the understanding and treatment of hearing loss. I seek to determine how sensory receptors within the inner ear respond to their micro-mechanical environment, and thus how disturbances in this environment lead to disruptions of the tuned capabilities of functional hearing. This unique approach provides a foundation for better understanding of how we hear and could suggest avenues for future biomedical interventions.

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
Project #
Application #
Study Section
Special Emphasis Panel (ZDC1-SRB-Z (24))
Program Officer
Sklare, Dan
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Weill Medical College of Cornell University
Schools of Medicine
New York
United States
Zip Code
Dow, Eliot; Jacobo, Adrian; Hossain, Sajjad et al. (2018) Connectomics of the zebrafish's lateral-line neuromast reveals wiring and miswiring in a simple microcircuit. Elife 7:
Azimzadeh, Julien B; Salvi, Joshua D (2017) Physiological Preparation of Hair Cells from the Sacculus of the American Bullfrog (Rana catesbeiana). J Vis Exp :
Gnedeva, Ksenia; Jacobo, Adrian; Salvi, Joshua D et al. (2017) Elastic force restricts growth of the murine utricle. Elife 6:
Milewski, Andrew R; Ó Maoiléidigh, Dáibhid; Salvi, Joshua D et al. (2017) Homeostatic enhancement of sensory transduction. Proc Natl Acad Sci U S A 114:E6794-E6803
Salvi, Joshua D; Ó Maoiléidigh, Dáibhid; Hudspeth, A J (2016) Identification of Bifurcations from Observations of Noisy Biological Oscillators. Biophys J 111:798-812
Salvi, Joshua D; Ó Maoiléidigh, Dáibhid; Fabella, Brian A et al. (2015) Control of a hair bundle's mechanosensory function by its mechanical load. Proc Natl Acad Sci U S A 112:E1000-9
Dow, Eliot; Siletti, Kimberly; Hudspeth, Albert J (2015) Cellular projections from sensory hair cells form polarity-specific scaffolds during synaptogenesis. Genes Dev 29:1087-94
Salvi, Joshua D (2014) Graphic tobacco warning labels - an improper solution? Lung Cancer (Auckl) 5:33-34
Riddle, Megan C; Lin, Jiahui; Steinman, Jonathan B et al. (2014) Incorporating the principles of the patient-centered medical home into a student-run free clinic. Adv Med Educ Pract 5:289-97