# Measuring and Modeling the Effects of Reticular Lamina Flexibility on Outer Hair Cell Bundle Phase and Cochlear Amplification

> **NIH NIH F31** · HARVARD MEDICAL SCHOOL · 2024 · $36,856

## Abstract

ABSTRACT
The mammalian auditory system has evolved into a biological marvel with high sensitivity that can largely be
traced to nonlinear amplification by the organ of Corti (OoC)—the sensory epithelium within the cochlea of the
inner ear. Despite decades of research, the inaccessibility of the inner ear’s bony capsule and the technological
challenges of measuring and modeling nanometer-scale vibrations in a multi-physics system have made it
difficult to uncover OoC structure-function relationships. However, increased computational capabilities and
novel imaging technologies such as optical coherence tomography (OCT) now make it possible to capture OoC
motion in more detail than ever before, which is revolutionizing our understanding of cochlear amplification. The
most well-understood aspect of amplification is the somatic motility of outer hair cells (OHCs), and recent data
measuring OoC motion across the three rows of OHCs suggests that the reticular lamina (RL) is flexible and not
a stiff plate as was thought for over a century. Our central hypothesis is that RL flexibility sets the phase of OHC
bundle motion and is therefore necessary for cochlear amplification. To test this hypothesis, we will measure
OoC motion from multiple angles from healthy cochleae of living, normal-hearing mice using a high-resolution
OCT system in both the lower-frequency apical region and higher-frequency basal region of mice. We will
measure distinct radial locations along the RL and along the junctions between OHCs and Deiters’ cells
corresponding to the three OHC rows, at multiple frequencies and sound pressure levels. We will also measure
along the basilar membrane (BM) to fully characterize RL motion in relation to the motion of the BM and other
OoC structures. These measurements will test our hypothesis by providing empirical evidence for the degree of
RL flexibility in the radial and transverse directions across different frequencies and levels at two different
cochlear locations. We will also use the measurements to develop detailed, multi-physics, finite-element cochlear
models, which will give us insight into the relationship between the RL and tectorial membrane and the drive to
OHC bundles. Both the apical and basal models will contain key elements of OoC cytoarchitecture including the
interdigitated Y-shape building blocks made from OHCs, Deiters’ cells, and the phalangeal processes of Deiters’
cells, sandwiched between the basilar membrane and the RL mosaic. We aim to produce motion in the models
comparable to post-mortem (passive) and in-vivo (active) OCT measurements and will investigate the effects of
RL stiffness on OHC-bundle phase and cochlear amplification. Completion of these aims will have wide-reaching
implications. Not only will this research uncover fundamental knowledge about the nature of hearing, but it has
the potential to contribute to improved understanding, diagnoses, and treatment of human cochlear pathologies.

## Key facts

- **NIH application ID:** 10769747
- **Project number:** 5F31DC021079-02
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** Gabriel Alberts
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $36,856
- **Award type:** 5
- **Project period:** 2023-03-01 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10769747

## Citation

> US National Institutes of Health, RePORTER application 10769747, Measuring and Modeling the Effects of Reticular Lamina Flexibility on Outer Hair Cell Bundle Phase and Cochlear Amplification (5F31DC021079-02). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10769747. Licensed CC0.

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