# Morphological and Molecular Development of Efferent Innervation of the Cochlea

> **NIH NIH F32** · HARVARD MEDICAL SCHOOL · 2021 · $70,458

## Abstract

Project Summary
Olivocochlear neurons (OCNs) reside in the auditory brainstem and project to the cochlea, providing efferent
innervation in addition to the afferent circuitry of the spiral ganglion neurons (SGNs), housed within the
cochlea. OCNs protect the cochlea from noise damage and modulate acoustic input, and alignment between the
afferent and efferent components of auditory circuitry is crucial for proper auditory functioning. OCNs are
composed of medial olivocochlear neurons (MOCs) and lateral olivocochlear neurons (LOCs), which innervate
the outer hair cells (OHCs) and SGNs, respectively. MOC axons arrive in the cochlea before LOCs and
transiently innervate inner hair cells (IHCs) during an important period of development of the SGN afferent
circuitry. MOCs are therefore in a prime position to influence both the development of SGNs and later-arriving
OCN axons.
A lack of genetic access to MOCs and LOCs has so far hindered progress in identifying the cell-cell interactions
between OCNs and SGNs during early cochlear development, leaving many open questions about how central
and peripheral components of the auditory system align. This research training plan will use newly identified
genetic tools to selectively label and perturb OCNs in order to address the hypothesis that early arriving OCN
axons interact with SGNs and IHCs to shape the development of cochlear circuitry. Aim 1 will use early
induction of recombination in RetCreER mice to sparsely and selectively label the first MOC axons to enter the
cochlea. Labeled OCN fibers and synapses will be analyzed to provide a detailed account of key interactions
between MOC axons and SGNs and IHCs. Aim 2 will first transcriptionally profile embryonic MOCs and LOCs
using single-cell RNA-sequencing to identify Ephs, ephrins, and other molecules that may guide OCN
development. Finally, efferent/afferent wiring will be assessed in EphA4 and ephrin-A5 mutants to shed light
on efferent pathfinding mechanisms and how EphA4/ephrin-A5 interactions mediate multiple aspects of
cochlear circuitry. Results from these studies will reveal important morphological and molecular interactions
between OCN axons and other cells in the cochlea that establish a functioning auditory circuit.
The research training plan will provide extensive training in the auditory system, molecular genetics
approaches, quantitative image analysis, and basic bioinformatics. Additionally, the training plan will offer
professional development opportunities, including mentoring students and presenting research at small group
meetings, departmental talks, and conferences. The skills developed under this plan will pave the way for an
independent research career in the field of auditory neurobiology, studying the role of axon-axon interactions
in the development of auditory circuitry.

## Key facts

- **NIH application ID:** 10174662
- **Project number:** 5F32DC019009-02
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** Austen Anne Sitko
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $70,458
- **Award type:** 5
- **Project period:** 2020-06-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10174662

## Citation

> US National Institutes of Health, RePORTER application 10174662, Morphological and Molecular Development of Efferent Innervation of the Cochlea (5F32DC019009-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10174662. Licensed CC0.

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