Ca 2+ -permeable AMPARs mediate glutamatergic transmission and excitotoxic damage at the hair cell ribbon synapse

Joy Y. Sebe, Soyoun Cho, Lavinia Sheets, Mark A. Rutherford, Henrique von Gersdorff, David W. Raible

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

We report functional and structural evidence for GluA2-lacking Ca 2+ -permeable AMPARs (CP-AMPARs) at the mature hair cell ribbon synapse. By using the methodological advantages of three species (of either sex), we demonstrate that CP-AMPARs are present at the hair cell synapse in an evolutionarily conserved manner. Via a combination of in vivo electrophysiological and Ca 2+ imaging approaches in the larval zebrafish, we show that hair cell stimulation leads to robust Ca 2+ influx into afferent terminals. Prolonged application of AMPA caused loss of afferent terminal responsiveness, whereas blocking CP-AMPARs protects terminals from excitotoxic swelling. Immuno his to chemical analysis of AMPAR subunits in mature rat cochlea show regions within synapses lacking the GluA2 subunit. Paired recordings from adult bullfrog auditory synapses demonstrate that CP-AMPARs mediate a major component of glutamatergic transmission. Together, our results support the importance of CP-AMPARs in mediating transmission at the hair cell ribbon synapse. Further, excess Ca 2+ entry via CP-AMPARs may underlie afferent terminal damage following excitotoxic challenge, suggesting that limiting Ca 2+ levels in the afferent terminal may protect against cochlear synaptopathy associated with hearing loss.

Original languageEnglish (US)
Pages (from-to)6162-6175
Number of pages14
JournalJournal of Neuroscience
Volume37
Issue number25
DOIs
StatePublished - Jun 21 2017

Fingerprint

Synapses
Cochlea
Rana catesbeiana
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
Zebrafish
Hearing Loss

Keywords

  • Cochlear synaptopathy
  • Excitotoxicity
  • GCaMP
  • Noise overexposure
  • Zebrafish

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Ca 2+ -permeable AMPARs mediate glutamatergic transmission and excitotoxic damage at the hair cell ribbon synapse . / Sebe, Joy Y.; Cho, Soyoun; Sheets, Lavinia; Rutherford, Mark A.; von Gersdorff, Henrique; Raible, David W.

In: Journal of Neuroscience, Vol. 37, No. 25, 21.06.2017, p. 6162-6175.

Research output: Contribution to journalArticle

Sebe, Joy Y. ; Cho, Soyoun ; Sheets, Lavinia ; Rutherford, Mark A. ; von Gersdorff, Henrique ; Raible, David W. / Ca 2+ -permeable AMPARs mediate glutamatergic transmission and excitotoxic damage at the hair cell ribbon synapse In: Journal of Neuroscience. 2017 ; Vol. 37, No. 25. pp. 6162-6175.
@article{7378c0c0d40e46a79f8a27bf9a564b49,
title = "Ca 2+ -permeable AMPARs mediate glutamatergic transmission and excitotoxic damage at the hair cell ribbon synapse",
abstract = "We report functional and structural evidence for GluA2-lacking Ca 2+ -permeable AMPARs (CP-AMPARs) at the mature hair cell ribbon synapse. By using the methodological advantages of three species (of either sex), we demonstrate that CP-AMPARs are present at the hair cell synapse in an evolutionarily conserved manner. Via a combination of in vivo electrophysiological and Ca 2+ imaging approaches in the larval zebrafish, we show that hair cell stimulation leads to robust Ca 2+ influx into afferent terminals. Prolonged application of AMPA caused loss of afferent terminal responsiveness, whereas blocking CP-AMPARs protects terminals from excitotoxic swelling. Immuno his to chemical analysis of AMPAR subunits in mature rat cochlea show regions within synapses lacking the GluA2 subunit. Paired recordings from adult bullfrog auditory synapses demonstrate that CP-AMPARs mediate a major component of glutamatergic transmission. Together, our results support the importance of CP-AMPARs in mediating transmission at the hair cell ribbon synapse. Further, excess Ca 2+ entry via CP-AMPARs may underlie afferent terminal damage following excitotoxic challenge, suggesting that limiting Ca 2+ levels in the afferent terminal may protect against cochlear synaptopathy associated with hearing loss.",
keywords = "Cochlear synaptopathy, Excitotoxicity, GCaMP, Noise overexposure, Zebrafish",
author = "Sebe, {Joy Y.} and Soyoun Cho and Lavinia Sheets and Rutherford, {Mark A.} and {von Gersdorff}, Henrique and Raible, {David W.}",
year = "2017",
month = "6",
day = "21",
doi = "10.1523/JNEUROSCI.3644-16.2017",
language = "English (US)",
volume = "37",
pages = "6162--6175",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "25",

}

TY - JOUR

T1 - Ca 2+ -permeable AMPARs mediate glutamatergic transmission and excitotoxic damage at the hair cell ribbon synapse

AU - Sebe, Joy Y.

AU - Cho, Soyoun

AU - Sheets, Lavinia

AU - Rutherford, Mark A.

AU - von Gersdorff, Henrique

AU - Raible, David W.

PY - 2017/6/21

Y1 - 2017/6/21

N2 - We report functional and structural evidence for GluA2-lacking Ca 2+ -permeable AMPARs (CP-AMPARs) at the mature hair cell ribbon synapse. By using the methodological advantages of three species (of either sex), we demonstrate that CP-AMPARs are present at the hair cell synapse in an evolutionarily conserved manner. Via a combination of in vivo electrophysiological and Ca 2+ imaging approaches in the larval zebrafish, we show that hair cell stimulation leads to robust Ca 2+ influx into afferent terminals. Prolonged application of AMPA caused loss of afferent terminal responsiveness, whereas blocking CP-AMPARs protects terminals from excitotoxic swelling. Immuno his to chemical analysis of AMPAR subunits in mature rat cochlea show regions within synapses lacking the GluA2 subunit. Paired recordings from adult bullfrog auditory synapses demonstrate that CP-AMPARs mediate a major component of glutamatergic transmission. Together, our results support the importance of CP-AMPARs in mediating transmission at the hair cell ribbon synapse. Further, excess Ca 2+ entry via CP-AMPARs may underlie afferent terminal damage following excitotoxic challenge, suggesting that limiting Ca 2+ levels in the afferent terminal may protect against cochlear synaptopathy associated with hearing loss.

AB - We report functional and structural evidence for GluA2-lacking Ca 2+ -permeable AMPARs (CP-AMPARs) at the mature hair cell ribbon synapse. By using the methodological advantages of three species (of either sex), we demonstrate that CP-AMPARs are present at the hair cell synapse in an evolutionarily conserved manner. Via a combination of in vivo electrophysiological and Ca 2+ imaging approaches in the larval zebrafish, we show that hair cell stimulation leads to robust Ca 2+ influx into afferent terminals. Prolonged application of AMPA caused loss of afferent terminal responsiveness, whereas blocking CP-AMPARs protects terminals from excitotoxic swelling. Immuno his to chemical analysis of AMPAR subunits in mature rat cochlea show regions within synapses lacking the GluA2 subunit. Paired recordings from adult bullfrog auditory synapses demonstrate that CP-AMPARs mediate a major component of glutamatergic transmission. Together, our results support the importance of CP-AMPARs in mediating transmission at the hair cell ribbon synapse. Further, excess Ca 2+ entry via CP-AMPARs may underlie afferent terminal damage following excitotoxic challenge, suggesting that limiting Ca 2+ levels in the afferent terminal may protect against cochlear synaptopathy associated with hearing loss.

KW - Cochlear synaptopathy

KW - Excitotoxicity

KW - GCaMP

KW - Noise overexposure

KW - Zebrafish

UR - http://www.scopus.com/inward/record.url?scp=85021154480&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85021154480&partnerID=8YFLogxK

U2 - 10.1523/JNEUROSCI.3644-16.2017

DO - 10.1523/JNEUROSCI.3644-16.2017

M3 - Article

C2 - 28539424

AN - SCOPUS:85021154480

VL - 37

SP - 6162

EP - 6175

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 25

ER -