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Localisation of glutamate receptors in developing cortical neurons in culture and relationship to susceptibility to excitotoxicity

journal contribution
posted on 2023-05-16, 19:23 authored by Anna KingAnna King, Chung, RS, James VickersJames Vickers, Tracey DicksonTracey Dickson
Overactivation of glutamate receptors leading to excitotoxicity has been implicated in the neurodegenerative alterations of a range of central nervous system (CNS) disorders. We have investigated the cell-type-specific changes in glutamate receptor localization in developing cortical neurons in culture, as well as the relationship between glutamate receptor subunit distribution with synapse formation and susceptibility to excitotoxicity. Glutamate receptor subunit clustering was present prior to the formation of synapses. However, different receptor types showed distinctive temporal patterns of subunit clustering, localization to spines, and apposition to presynaptic terminals. N-methyl-D-aspartate (NMDA) receptor subunit immunolabelling was present in puncta along dendrites prior to the formation of synapses, with relatively little localization to spines. Vulnerability to NMDA receptor-mediated excitotoxicity occurred before receptor subunits became localized in apposition to presynaptic terminals. Clustering of α-amino-3-hydroxy-5-methyl-4- isoxazole propionic acid (AMPA) receptors occurred concurrently with development of vulnerability to excitotoxicity and was related to localization of AMPA receptors at synapses and in spines. Different AMPA receptor subunits demonstrated cell-type-specific localization as well as distribution to spines, dendrites, and extrasynaptic subunit clusters. A subclass of neurons demonstrated substantial perineuronal synaptic innervation, and these neurons expressed relatively high levels of GluR1 and/or GluR4 at receptor puncta, indicating the presence of calcium-permeable AMPA receptors and suggesting alternative synaptic signalling mechanisms and vulnerability to excitotoxicity. These data demonstrate the relationship between glutamate receptor subunit expression and localization with synaptogenesis and development of neuronal susceptibility to excitotoxicity. These data also suggest that excitotoxicity can be mediated through extrasynaptic receptor subunit complexes along dendrites. © 2006 Wiley-Liss, Inc.

History

Publication title

Journal of Comparative Neurology

Volume

498

Pagination

277-294

ISSN

0021-9967

Department/School

Menzies Institute for Medical Research

Publisher

NJ, USA

Place of publication

DIV JOHN WILEY & SONS INC

Repository Status

  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified

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