Auditory hair cells and spiral ganglion neurons regenerate synapses with refined release properties in vitro.


Journal

Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876

Informations de publication

Date de publication:
30 Jul 2024
Historique:
medline: 26 7 2024
pubmed: 26 7 2024
entrez: 26 7 2024
Statut: ppublish

Résumé

Ribbon synapses between inner hair cells (IHCs) and type I spiral ganglion neurons (SGNs) in the inner ear are damaged by noise trauma and with aging, causing "synaptopathy" and hearing loss. Cocultures of neonatal denervated organs of Corti and newly introduced SGNs have been developed to find strategies for improving IHC synapse regeneration, but evidence of the physiological normality of regenerated synapses is missing. This study utilizes IHC optogenetic stimulation and SGN recordings, showing that, when P3-5 denervated organs of Corti are cocultured with SGNs, newly formed IHC/SGN synapses are indeed functional, exhibiting glutamatergic excitatory postsynaptic currents. When using older organs of Corti at P10-11, synaptic activity probed by deconvolution showed more mature release properties, closer to the specialized mode of IHC synaptic transmission crucial for coding the sound signal. This functional assessment of newly formed IHC synapses developed here, provides a powerful tool for testing approaches to improve synapse regeneration.

Identifiants

pubmed: 39058581
doi: 10.1073/pnas.2315599121
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

e2315599121

Subventions

Organisme : HHS | NIH | National Institute on Deafness and Other Communication Disorders (NIDCD)
ID : R01DC006476
Organisme : HHS | NIH | National Institute on Deafness and Other Communication Disorders (NIDCD)
ID : R01DC007174

Déclaration de conflit d'intérêts

Competing interests statement:The authors declare no competing interest.

Auteurs

Philippe F Y Vincent (PFY)

The Center for Hearing and Balance, The Johns Hopkins School of Medicine, Baltimore, MD 21205.
Department of Otolaryngology Head and Neck Surgery, The Johns Hopkins School of Medicine, Baltimore, MD 21205.

Eric D Young (ED)

The Center for Hearing and Balance, The Johns Hopkins School of Medicine, Baltimore, MD 21205.
Department of Otolaryngology Head and Neck Surgery, The Johns Hopkins School of Medicine, Baltimore, MD 21205.
Department of Neuroscience, The Johns Hopkins School of Medicine, Baltimore, MD 21205.
Department of Biomedical Engineering, The Johns Hopkins School of Medicine, Baltimore, MD 21205.

Albert S B Edge (ASB)

Department of Otolaryngology, Harvard Medical School, Boston, MA 02115.
Eaton-Peabody Laboratory, Massachusetts Eye and Ear, Boston, MA 02114.
Program in Speech and Hearing Bioscience and Technology, Harvard Medical School, Boston, MA 02115.
Harvard Stem Cell Institute, Cambridge, MA 02139.

Elisabeth Glowatzki (E)

The Center for Hearing and Balance, The Johns Hopkins School of Medicine, Baltimore, MD 21205.
Department of Otolaryngology Head and Neck Surgery, The Johns Hopkins School of Medicine, Baltimore, MD 21205.
Department of Neuroscience, The Johns Hopkins School of Medicine, Baltimore, MD 21205.

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Classifications MeSH