Delayed expression of activity-dependent gating switch in synaptic AMPARs at a central synapse

Lee Stephen Lesperance, Yi Mei Yang, Lu Yang Wang

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Developing central synapses exhibit robust plasticity and undergo experience-dependent remodeling. Evidently, synapses in sensory systems such as auditory brainstem circuits mature rapidly to achieve high-fidelity neurotransmission for sound localization. This depends on a developmental switch in AMPAR composition from slow-gating GluA1-dominant to fast-gating GluA4-dominant, but the mechanisms underlying this switch remain unknown. We hypothesize that patterned stimuli mimicking spontaneous/sound evoked activity in the early postnatal stage drives this gating switch. We examined activity-dependent changes in evoked and miniature excitatory postsynaptic currents (eEPSCs and mEPSCs) at the calyx of Held synapse by breaking through the postsynaptic membrane at different time points following 2 min of theta burst stimulation (TBS) to afferents in mouse brainstem slices. We found the decay time course of eEPSCs accelerated, but this change was not apparent until > 30 min after TBS. Histogram analyses of the decay time constants of mEPSCs for naive and tetanized synapses revealed two populations centered around τfast ≈ 0.4 and 0.8 ms, but the relative weight of the τ0.4 population over the τ0.8 population increased significantly only in tetanized synapses. Such changes are blocked by NMDAR or mGluR1/5 antagonists or inhibitors of CaMKII, PKC and protein synthesis, and more importantly precluded in GluA4-/- synapses, suggesting GluA4 is the substrate underlying the acceleration. Our results demonstrate a novel form of plasticity working through NMDAR and mGluR activation to trigger a gating switch of AMPARs with a temporally delayed onset of expression, ultimately enhancing the development of high-fidelity synaptic transmission.

Original languageEnglish (US)
Article number6
JournalMolecular brain
Issue number1
StatePublished - Jan 15 2020

Bibliographical note

Funding Information:
This work was supported by individual operating grants from the Canadian Institute of Health Research (MOP-81159; MOP-77610, PJT-156034) and Canada Research Chair Program.

Publisher Copyright:
© 2020 The Author(s).


  • AMPAR subunit composition
  • Activity-dependent plasticity
  • Calyx of held-MNTB synapse
  • Developing plasticity
  • Synaptic transmission


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