Nuritova, F. and Frenguelli, Bruno G. (2012) Putative depolarisation-induced retrograde signalling accelerates the repeated hypoxic depression of excitatory synaptic transmission in area CA1 of rat hippocampus via group I metabotropic glutamate receptors. Neuroscience, Vol.222 . pp. 159-172. doi:10.1016/j.neuroscience.2012.07.034 ISSN 0306-4522.
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Abstract
Excitatory synaptic transmission in area CA1 of the mammalian hippocampus is rapidly depressed during hypoxia. The depression is largely attributable to an increase in extracellular adenosine and activation of inhibitory adenosine A(1) receptors on presynaptic glutamatergic terminals. However, sequential exposure to hypoxia results in a slower subsequent hypoxic depression of excitatory synaptic transmission, a phenomenon we have previously ascribed to a reduction in the release of extracellular adenosine. In the present study we show that this delayed depression of excitatory postsynaptic currents (EPSCs) to repeated hypoxia can be reversed by a period of postsynaptic depolarisation delivered to an individual CA1 neuron, under whole-cell voltage clamp, between two periods of hypoxia. The depolarisation-induced acceleration of the hypoxic depression of the EPSC is dependent upon postsynaptic Ca2+ influx, the activation of PKC and is blocked by intracellular application of GDP-beta-S and N-ethylmaleimide (NEM), inhibitors of membrane fusion events. In addition, the acceleration of the hypoxic depression of the EPSC was prevented by the GI mGluR antagonist AIDA, but not by the CBI cannabinoid receptor antagonist AM251. Our results suggest a process initiated in the postsynaptic cell that can influence glutamate release during subsequent metabolic stress. This may reflect a novel neuroprotective strategy potentially involving retrograde release of adenosine and/or glutamate. (C) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.
| Item Type: | Journal Article |
|---|---|
| Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) |
| Journal or Publication Title: | Neuroscience |
| Publisher: | Elsevier |
| ISSN: | 0306-4522 |
| Official Date: | 11 October 2012 |
| Dates: | Date Event 11 October 2012 Published |
| Volume: | Vol.222 |
| Page Range: | pp. 159-172 |
| DOI: | 10.1016/j.neuroscience.2012.07.034 |
| Status: | Peer Reviewed |
| Publication Status: | Published |
| Access rights to Published version: | Restricted or Subscription Access |
| URI: | https://wrap.warwick.ac.uk/52308/ |
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