Sensory neuron diversity in the inner ear is shaped by activity
Open accessAbstract
In the auditory system, type I spiral ganglion neurons (SGNs) convey complex acoustic information from inner hair cells (IHCs) to the brainstem. Although SGNs exhibit variation in physiological and anatomical properties, it is unclear which features are endogenous and which reflect input from synaptic partners. Using single-cell RNA sequencing, we derived a molecular classification of mouse type I SGNs comprising three subtypes that express unique combinations of Ca 2+ binding proteins, ion channel regulators, guidance molecules, and transcription factors. Based on connectivity and susceptibility to age-related loss, these subtypes correspond to those defined physiologically. Additional intrinsic differences among subtypes and across the tonotopic axis highlight an unexpectedly active role for SGNs in auditory processing. SGN identities emerge postnatally and are disrupted in a mouse model of deafness that lacks IHC-driven activity. These results elucidate the range, nature, and origins of SGN diversity, with implications for treatment of congenital deafness.
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Type II afferents express neuropeptides such as CGRP, which in somatic C-fibers modulates the activity of immune cells that proliferate after trauma.
“Type II afferents express neuropeptides such as CGRP (37, 38, 54), which in somatic C-fibers (55) modulates the activity of immune cells that proliferate after trauma (56).”
From Damage-evoked signals in cochlear neurons and supporting cells (2024) · cites this paper as [54]
Citation 54 is attached to the claim that Type II afferents express neuropeptides such as CGRP. The Results section on Type I and Type II SGN molecular differences reports other Type II-enriched molecules but does not identify CGRP or a neuropeptide; searches for CGRP, Calca, and calcitonin gene-related peptide found no supporting passage. The statements about somatic C-fibers and immune cells have separate citations (55 and 56). (LLM, conf=0.72)
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References 74 · Cited by 432
- Authors
- Shrestha, B. R., Chia, C., Wu, L., Kujawa, S. G., Liberman, M. C., & Goodrich, L. V.
- Affiliations
- Harvard University (US)
- Massachusetts Eye and Ear Infirmary (US)
- Corresponding author
- Goodrich, Lisa V.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2018-08
- Volume
- 174
- Issue
- 5
- Pages
- 1229-1246.e17
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC6150604
- OpenAlex
- W2886288118
- Cited by
- 432
- References
- 74
- Citations by year
- 2026: 43 · 2025: 53 · 2024: 60 · 2023: 66 · 2022: 43 · 2021: 63 · 2020: 54 · 2019: 39 · 2018: 10
- FWCI
- 26.75
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NCRR (1S10RR028832-01)
- Lefler Research Grant
- Harvard Brain Science Initiative Collaborative Seed Grant
- Leonard and Isabelle Goldenson Postdoctoral Fellowship
- NIH (T32 AG 222-24, 5 T32 NS007484-14, 5F32DC014371, R01 DC000188, DC009223)
- Topics
- Life Sciences › Neuroscience › Sensory Systems › Hearing, Cochlea, Tinnitus, Genetics
- Life Sciences › Neuroscience › Neurology › Vestibular and auditory disorders
- Life Sciences › Neuroscience › Cognitive Neuroscience › Hearing Loss and Rehabilitation
- Keywords
- inner hair cells, auditory system, molecular classification, calcium-binding proteins, guidance molecules, transcription factors, age-related hearing loss, congenital hearing loss, single-cell RNA sequencing
- MeSH terms
- Animals, Cochlea, Deafness, Female, Hair Cells, Auditory, Inner, Ear, Inner, Male, Mice, Inbred C57BL, Synaptic Transmission, Sensory Receptor Cells, Spiral Ganglion, Sequence Analysis, RNA, Transgenes, Amino Acid Transport Systems, Acidic, Mice, Calbindin 2
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