Presynaptic diversity revealed by Ca 2+ -permeable AMPA receptors at the calyx of held synapse

Brendan Lujan, Andre Dagostin, Henrique Von Gersdorff

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

GluA2-lacking Ca 2+ -permeable AMPARs (CP-AMPARs) play integral roles in synaptic plasticity and can mediate excitotoxic cellular signaling at glutamatergic synapses. However, the developmental profile of functional CP-AMPARs at the auditory brainstem remains poorly understood. Through a combination of electrophysiological and live-cell Ca 2+ imaging from mice of either sex, we show that the synaptic release of glutamate from the calyx of Held nerve terminal activatesCP-AMPARsin the principal cells of the medial nucleus of the trapezoid body in the brainstem. This leads to significant Ca 2+ influx through these receptors before the onset of hearing at postnatal day 12 (P12). Using a selective open channel blocker of CP-AMPARs, IEM-1460, we estimate that 80% of the AMPAR population are permeable to Ca 2+ at immature P4-P5 synapses. However, after the onset of hearing, Ca 2+ influx through these receptors was greatly reduced. We estimate that CP-AMPARs comprise approximately 40% and 33% of the AMPAR population at P18 -P22 and P30 -P34, respectively. By quantifying the rate of EPSC block by IEM-1460, we found an increased heterogeneity in glutamate release probability for adult-like calyces (P30 -P34). Using tetraethylammonium (TEA), a presynaptic potassium channel blocker, we show that the apparent reduction of CP-AMPARs in more mature synapses is not a consequence of presynaptic action potential (AP) speeding. Finally, through postsynaptic AP recordings, we show that inhibition of CP-AMPARs reduces spike fidelity in juvenile synapses, but not in more mature synapses. We conclude that the expression of functional CP-AMPARs declines over early postnatal development in the calyx of Held synapse.

Original languageEnglish (US)
Pages (from-to)2981-2994
Number of pages14
JournalJournal of Neuroscience
Volume39
Issue number16
DOIs
StatePublished - Apr 17 2019

Fingerprint

AMPA Receptors
Synapses
Hearing
Action Potentials
Brain Stem
Glutamic Acid
Potassium Channel Blockers
Synaptic Potentials
Neuronal Plasticity
Tetraethylammonium
Cell Nucleus
Population
(2-azidomethyl)phenylacetyl

Keywords

  • AMPA
  • Auditory brainstem
  • Calyx of Held
  • EPSC
  • Laser confocal ca imaging
  • MNTB

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Presynaptic diversity revealed by Ca 2+ -permeable AMPA receptors at the calyx of held synapse . / Lujan, Brendan; Dagostin, Andre; Von Gersdorff, Henrique.

In: Journal of Neuroscience, Vol. 39, No. 16, 17.04.2019, p. 2981-2994.

Research output: Contribution to journalArticle

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