Glutamate-induced depression of EPSP–spike coupling in rat hippocampal CA1 neurons and modulation by adenosine receptors

Ferguson, A.L. and Stone, T.W. (2010) Glutamate-induced depression of EPSP–spike coupling in rat hippocampal CA1 neurons and modulation by adenosine receptors. European Journal of Neuroscience, 31(7), pp. 1208-1218. (doi: 10.1111/j.1460-9568.2010.07157.x)

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The presence of high concentrations of glutamate in the extracellular fluid following brain trauma or ischaemia may contribute substantially to subsequent impairments of neuronal function. In this study, glutamate was applied to hippocampal slices for several minutes, producing over-depolarization, which was reflected in an initial loss of evoked population potential size in the CA1 region. Orthodromic population spikes recovered only partially over the following 60 min, whereas antidromic spikes and excitatory postsynaptic potentials (EPSPs) showed greater recovery, implying a change in EPSP–spike coupling (E–S coupling), which was confirmed by intracellular recording from CA1 pyramidal cells. The recovery of EPSPs was enhanced further by dizocilpine, suggesting that the long-lasting glutamate-induced change in E–S coupling involves NMDA receptors. This was supported by experiments showing that when isolated NMDA-receptor-mediated EPSPs were studied in isolation, there was only partial recovery following glutamate, unlike the composite EPSPs. The recovery of orthodromic population spikes and NMDA-receptor-mediated EPSPs following glutamate was enhanced by the adenosine A1 receptor blocker DPCPX, the A2A receptor antagonist SCH58261 or adenosine deaminase, associated with a loss of restoration to normal of the glutamate-induced E–S depression. The results indicate that the long-lasting depression of neuronal excitability following recovery from glutamate is associated with a depression of E–S coupling. This effect is partly dependent on activation of NMDA receptors, which modify adenosine release or the sensitivity of adenosine receptors. The results may have implications for the use of A1 and A2A receptor ligands as cognitive enhancers or neuroprotectants.

Item Type:Articles
Additional Information:The definitive version is available at
Keywords:Adenosine, EPSPs, E–S coupling, glutamate, hippocampus, population spikes, purines
Glasgow Author(s) Enlighten ID:Stone, Professor Trevor and Ferguson, Dr Alexandra
Authors: Ferguson, A.L., and Stone, T.W.
Subjects:R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
College/School:College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
Journal Name:European Journal of Neuroscience
Journal Abbr.:Europ. J. Neurosci.
ISSN (Online):1460-9568
Published Online:19 March 2010
Copyright Holders:Copyright © 2010 Wiley-Blackwell
First Published:First published in European Journal of Neuroscience 31(7):1208-1218
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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