Auditory hair cells and spiral ganglion neurons regenerate synapses with refined release properties in vitro-Reference-Cited by-同舟云学术

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

Published:2024-07-26 Issue:31 Volume:121 Page:
ISSN:0027-8424
Container-title:Proceedings of the National Academy of Sciences
language:en
Short-container-title:Proc. Natl. Acad. Sci. U.S.A.

Author:

Vincent Philippe F. Y.¹²^ORCID,Young Eric D.¹²³⁴^ORCID,Edge Albert S. B.⁵⁶⁷⁸^ORCID,Glowatzki Elisabeth¹²³^ORCID

Affiliation:

1. The Center for Hearing and Balance, The Johns Hopkins School of Medicine, Baltimore, MD 21205

2. Department of Otolaryngology Head and Neck Surgery, The Johns Hopkins School of Medicine, Baltimore, MD 21205

3. Department of Neuroscience, The Johns Hopkins School of Medicine, Baltimore, MD 21205

4. Department of Biomedical Engineering, The Johns Hopkins School of Medicine, Baltimore, MD 21205

5. Department of Otolaryngology, Harvard Medical School, Boston, MA 02115

6. Eaton-Peabody Laboratory, Massachusetts Eye and Ear, Boston, MA 02114

7. Program in Speech and Hearing Bioscience and Technology, Harvard Medical School, Boston, MA 02115

8. Harvard Stem Cell Institute, Cambridge, MA 02139

Abstract

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.

Funder

HHS | NIH | National Institute on Deafness and Other Communication Disorders

Publisher

Proceedings of the National Academy of Sciences

Link

https://pnas.org/doi/pdf/10.1073/pnas.2315599121

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