Auditory hair cells and spiral ganglion neurons regenerate synapses with refined release properties in vitro.
Animals
Spiral Ganglion
/ cytology
Synapses
/ physiology
Mice
Hair Cells, Auditory, Inner
/ physiology
Synaptic Transmission
/ physiology
Neurons
/ physiology
Regeneration
/ physiology
Hair Cells, Auditory
/ physiology
Coculture Techniques
/ methods
Optogenetics
/ methods
Nerve Regeneration
/ physiology
Excitatory Postsynaptic Potentials
/ physiology
Organ of Corti
/ physiology
hair cell ribbon synapses
optogenetics
postsynaptic currents
regeneration
type-I spiral ganglion neurons
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
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
e2315599121Subventions
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.