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


King, AE and Chung, RS and Vickers, JC and Dickson, TC, Localisation of glutamate receptors in developing cortical neurons in culture and relationship to susceptibility to excitotoxicity, Journal of Comparative Neurology, 498, (2) pp. 277-294. ISSN 0021-9967 (2006) [Refereed Article]

DOI: doi:10.1002/cne.21053


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.

Item Details

Item Type:Refereed Article
Research Division:Biomedical and Clinical Sciences
Research Group:Neurosciences
Research Field:Central nervous system
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:King, AE (Professor Anna King)
UTAS Author:Chung, RS (Associate Professor Roger Chung)
UTAS Author:Vickers, JC (Professor James Vickers)
UTAS Author:Dickson, TC (Professor Tracey Dickson)
ID Code:45094
Year Published:2006
Web of Science® Times Cited:40
Deposited By:Menzies Institute for Medical Research
Deposited On:2007-07-06
Last Modified:2007-07-06

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