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.
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.
authors.affiliation: Department of Otolaryngology, University of Pittsburgh Medical School, BST3 Building, 3501 Fifth Avenue #10016, Pittsburgh, PA, 15261, USA. mer@pitt.edu.|Department of Neurobiology, University of Pittsburgh, Pittsburgh, PA, USA. mer@pitt.edu.|Center for the Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, PA, USA. mer@pitt.edu.
authors.forename: María E
authors.initials: ME
authors.lastname: Rubio
authors.affiliation: Division of Interdisciplinary Medical Science, Tohoku University, Sendai, Japan.
authors.forename: Ko
authors.initials: K
authors.lastname: Matsui
authors.affiliation: Department of Brain Structure and Function, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
authors.forename: Yugo
authors.initials: Y
authors.lastname: Fukazawa
authors.affiliation: Max Planck Florida Institute, Jupiter, FL, USA.
authors.forename: Naomi
authors.initials: N
authors.lastname: Kamasawa
authors.affiliation: IST Austria, 3400, Klosterneuburg, Austria.
authors.forename: Harumi
authors.initials: H
authors.lastname: Harada
authors.affiliation: Department of Biochemistry, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Itakura
authors.affiliation: School of Physiology, Pharmacology and Neuroscience, University of Bristol, Biomedical Sciences Building, Bristol, BS8 1TD, UK.
authors.forename: Elek
authors.initials: E
authors.lastname: Molnár
authors.affiliation: Niigata University Brain Research Institute, Niigata, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Abe
authors.affiliation: Niigata University Brain Research Institute, Niigata, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Sakimura
authors.affiliation: IST Austria, 3400, Klosterneuburg, Austria.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Shigemoto
mesh_terms: D000818:Animals; D003056:Cochlear Nerve / Q000378:metabolism* / Q000648:ultrastructure; D017626:Cochlear Nucleus / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009434:Neural Pathways / Q000378:metabolism; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D021122:Protein Subunits; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D021122:Protein Subunits; D018091:Receptors, AMPA; C104723:glutamate receptor ionotropic, AMPA 3; C104724:glutamate receptor ionotropic, AMPA 4
keywords: Bushy cells; Electron microscopy; Freeze-fracture replica immunolabeling; Fusiform cells; Postsynaptic density; Synapses; Ventral cochlear nucleus