# Diversification of spiral ganglion neurons during development and in maturity

> **NIH NIH R21** · MASSACHUSETTS EYE AND EAR INFIRMARY · 2022 · $168,000

## Abstract

PROJECT ABSTRACT
Neural signals generated by inner hair cells (IHCs) are transmitted to higher brain center by a
functionally heterogeneous population of Type I spiral ganglion neurons (SGNs) in the inner ear.
Although Type I SGNs have been grouped into three physiological classes based on basal firing
rates, in the absence of molecular correlates, it has been difficult to study their development or
the basis of their differential vulnerability to acoustic overexposure. We recently conducted
single cell RNA-sequencing (scRNA-seq) and uncovered three broad Type I SGN molecular
subtypes that exhibit the same distinctions in peripheral anatomy and synaptic features found
among physiologically defined subgroups. In addition, we found that refinement of molecular
segregation, which is apparent shortly after birth, depends on spontaneous activity in the first
postnatal week. Some evidence, however, support a model in which the earliest molecular
segregation of Type I SGNs occurs embryonically, perhaps independent of activity. Here we
propose to study the early developmental appearance of SGN identities and their malleability in
adulthood using a transcriptome-based approach. In Aim 1, we investigate emergence of
molecular heterogeneity at embryonic stages and test the requirement of IHCs for this process.
In Aim 2, we determine the temporal window over which Type I SGNs undergo changes in
molecular identity upon loss of IHC-driven excitation and seek to identify a transcription factor
code that can mediate switching of subtype molecular identity in mature SGNs. Together, we
anticipate that completion of these aims will facilitate hypothesis-driven inquiries into the
mechanisms underlying early segregation of SGN identities, and inform approaches to
manipulate the molecular profiles of SGNs in adulthood. Our long-term goal is to gain a
mechanistic understanding of how extrinsic effectors influence cell-intrinsic programs to
generate distinct SGN identities during development and utilize that conceptual framework to
alter gene expression states in mature neurons toward therapeutic end goals.

## Key facts

- **NIH application ID:** 10320387
- **Project number:** 5R21DC018356-04
- **Recipient organization:** MASSACHUSETTS EYE AND EAR INFIRMARY
- **Principal Investigator:** Brikha Raj Shrestha
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $168,000
- **Award type:** 5
- **Project period:** 2020-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10320387

## Citation

> US National Institutes of Health, RePORTER application 10320387, Diversification of spiral ganglion neurons during development and in maturity (5R21DC018356-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10320387. Licensed CC0.

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