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


Author(s): Rubio, María E; Matsui, Ko; Fukazawa, Yugo; Kamasawa, Naomi; Harada, Harumi; Itakura, Makoto; Molnár, Elek; Abe, Manabu; Sakimura, Kenji; Shigemoto, Ryuichi
Article Title: The number and distribution of AMPA receptor channels containing fast kinetic GluA3 and GluA4 subunits at auditory nerve synapses depend on the target cells
Affiliation IST Austria
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. 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 AN-BC synapses. The central distribution of AMPARs is absent in GluA3-knockout mice, and gold particles are evenly distributed along the postsynaptic density. 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.
Keywords: Synapses; Electron microscopy; postsynaptic density; Ventral cochlear nucleus; bushy cells; fusiform cells; freeze-fracture replica immunolabeling
Journal Title: Brain Structure and Function
Volume: 222
Issue 8
ISSN: 1863-2661
Publisher: Springer  
Date Published: 2017-11-01
Start Page: 3375
End Page: 3393
Copyright Statement: CC BY 4.0
URL:
DOI: 10.1007/s00429-017-1408-0
Notes: The authors thank Mitsuru Ikeda for his techni- cal assistance with sample preparation. We also thank Dr. T. Shigeoka and Dr. Y. Ishida for their gift of the UPATrap vector. This research was supported by Grants from the NIH (NIDC 013048 to M.E.R.) and the Biotechnology and Biological Sciences Research Council, UK (Grant BB/J015938/1 to E.M.).
Open access: yes (OA journal)