Target- and input-dependent organization of AMPA and NMDA receptors in synaptic connections of the cochlear nucleus

Authors

  • María E Rubio,

    Corresponding author
    1. Department of Otolaryngology, University of Pittsburgh, Pittsburgh, PA, USA
    2. Department of Neurobiology, University of Pittsburgh, PA, USA
    • Correspondence to: María E. Rubio, MD, PhD, Department of Otolaryngology and Neurobiology, University of Pittsburgh Medical School, BST3 Bldg., 3501 Fifth Ave. #10015, Pittsburgh, PA 15261. E-mail: mer@pitt.edu

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  • Yugo Fukazawa,

    1. Division Cerebral Structure NIPS, Okazaki, Japan
    Current affiliation:
    1. Division of Cell Biology and Neuroscience, Faculty of Medical Science, University of Fukui, Fukui, Japan
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  • Naomi Kamasawa,

    1. Division Cerebral Structure NIPS, Okazaki, Japan
    Current affiliation:
    1. Max Planck Institute at Florida, Jupiter, FL, USA
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  • Cheryl Clarkson,

    1. Department of Otolaryngology, University of Pittsburgh, Pittsburgh, PA, USA
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  • Elek Molnár,

    1. School of Physiology and Pharmacology, University of Bristol, Bristol BS8 1TD, UK
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  • Ryuichi Shigemoto

    1. Division Cerebral Structure NIPS, Okazaki, Japan
    2. IST Austria, Klosterneuburg, Austria
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ABSTRACT

We examined the synaptic structure, quantity, and distribution of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)- and N-methyl-D-aspartate (NMDA)-type glutamate receptors (AMPARs and NMDARs, respectively) in rat cochlear nuclei by a highly sensitive freeze-fracture replica labeling technique. Four excitatory synapses formed by two distinct inputs, auditory nerve (AN) and parallel fibers (PF), on different cell types were analyzed. These excitatory synapse types included AN synapses on bushy cells (AN-BC synapses) and fusiform cells (AN-FC synapses) and PF synapses on FC (PF-FC synapses) and cartwheel cell spines (PF-CwC synapses). Immunogold labeling revealed differences in synaptic structure as well as AMPAR and NMDAR number and/or density in both AN and PF synapses, indicating a target-dependent organization. The immunogold receptor labeling also identified differences in the synaptic organization of FCs based on AN or PF connections, indicating an input-dependent organization in FCs. Among the four excitatory synapse types, the AN-BC synapses were the smallest and had the most densely packed intramembrane particles (IMPs), whereas the PF-CwC synapses were the largest and had sparsely packed IMPs. All four synapse types showed positive correlations between the IMP-cluster area and the AMPAR number, indicating a common intrasynapse-type relationship for glutamatergic synapses. Immunogold particles for AMPARs were distributed over the entire area of individual AN synapses; PF synapses often showed synaptic areas devoid of labeling. The gold-labeling for NMDARs occurred in a mosaic fashion, with less positive correlations between the IMP-cluster area and the NMDAR number. Our observations reveal target- and input-dependent features in the structure, number, and organization of AMPARs and NMDARs in AN and PF synapses. J. Comp. Neurol. 522:4023–4042, 2014. © 2014 Wiley Periodicals, Inc.

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