Abstract
We report functional and structural evidence for GluA2-lacking Ca2+-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 Ca2+ imaging approaches in the larval zebrafish, we show that hair cell stimulation leads to robust Ca2+ 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 Ca2+ entry via CP-AMPARs may underlie afferent terminal damage following excitotoxic challenge, suggesting that limiting Ca2+ levels in the afferent terminal may protect against cochlear synaptopathy associated with hearing loss.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 6162-6175 |
| Number of pages | 14 |
| Journal | Journal of Neuroscience |
| Volume | 37 |
| Issue number | 25 |
| DOIs | |
| State | Published - Jun 21 2017 |
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Keywords
- Cochlear synaptopathy
- Excitotoxicity
- GCaMP
- Noise overexposure
- Zebrafish
ASJC Scopus subject areas
- Neuroscience(all)
Cite this
Ca2+-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 journal › Article
}
TY - JOUR
T1 - Ca2+-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 Ca2+-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 Ca2+ imaging approaches in the larval zebrafish, we show that hair cell stimulation leads to robust Ca2+ 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 Ca2+ entry via CP-AMPARs may underlie afferent terminal damage following excitotoxic challenge, suggesting that limiting Ca2+ levels in the afferent terminal may protect against cochlear synaptopathy associated with hearing loss.
AB - We report functional and structural evidence for GluA2-lacking Ca2+-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 Ca2+ imaging approaches in the larval zebrafish, we show that hair cell stimulation leads to robust Ca2+ 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 Ca2+ entry via CP-AMPARs may underlie afferent terminal damage following excitotoxic challenge, suggesting that limiting Ca2+ 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 -