The number and distribution of AMPA receptor channels containing fast kinetic GluA3 and GluA4 subunits at auditory nerve synapses depend on the target cells

Maria Rubio, Ko Matsui, Yugo Fukazawa, Naomi Kamasawa, Harumi Harada, Makoto Itakura, Elek Molnar, Manabu Abe, Kenji Sakimura, Ryuichi Shigemoto

Research output: Contribution to journalArticle (Academic Journal)peer-review

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Abstract

The neurotransmitter receptor subtype, number, density and distribution relative to the location of transmitter release sites are key determinants of signal transmission. AMPA-type ionotropic glutamate receptors (AMPARs) containing GluA3 and GluA4 subunits are prominently expressed in subsets of neurons capable of firing action potentials at high frequencies, such as auditory relay neurons. The auditory nerve (AN) forms glutamatergic synapses on two types of relay neurons, bushy cells (BCs) and fusiform cells (FCs) of the cochlear nucleus. AN-BC and AN-FC synapses have distinct kinetics; thus, we investigated whether the number, density and localization of GluA3 and GluA4 subunits in these synapses are differentially organized using quantitative freeze-fracture replica immunogold labeling (FRIL). We identify a positive correlation between the number of AMPARs and the size of AN-BC and AN-FC synapses. Both types of AN synapses have similar numbers of AMPARs; however, the AN-BC have a higher density of AMPARs than AN-FC synapses because the AN-BC synapses are smaller. A higher number and density of GluA3 subunits are observed at AN-BC synapses, whereas a higher number and density of GluA4 subunits are observed at AN-FC synapses. The intrasynaptic distribution of immunogold labeling revealed that AMPAR subunits, particularly GluA3, are concentrated at the center of the ANBC synapses. The central distribution of AMPARs is absent in GluA3-knockout mice, and gold particles are evenly distributed along the postsynaptic density (PSD). GluA4 gold labeling was homogenously distributed along both synapse types. Thus, GluA3 and GluA4 subunits are distributed at AN synapses in a target-cell-dependent manner.
Original languageEnglish
Pages (from-to)3375–3393
Number of pages19
JournalBrain Structure and Function
Volume222
Issue number8
Early online date10 Apr 2017
DOIs
Publication statusPublished - Nov 2017

Bibliographical note

20 March 2017

Keywords

  • Electron microscopy
  • Ventral cochlear nucleus
  • Synapses
  • Bushy cells
  • Fusiform cells
  • Postsynaptic density
  • Freeze-fracture replica immunolabeling

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