期刊
NEUROPHARMACOLOGY
卷 65, 期 -, 页码 114-122出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2012.09.016
关键词
Calcium-permeable AMPA receptors; Adenosine A(2A) receptors; i-LTP; CA1 neurons
资金
- FCT [SFRH/BD/27661/2006, SFRH/BD/60386/2009, PTDC/SAU-NMU/110838/2009]
- Fundação para a Ciência e a Tecnologia [SFRH/BD/60386/2009] Funding Source: FCT
Long lasting enhancement of synaptic transmission can be triggered by brief bursts of afferent stimulation, underlying long-term potentiation (LTP), and also by brief ischemia in a process known as i-LTP. The extent to which LTP and i-LTP rely on comparable cellular mechanisms remains unclear. Under physiological conditions, LTP induction drives transient expression of calcium-permeable AMPARs (CP-AMPARs) at synapses, whose ability to undergo plasticity is primed by endogenous activation of adenosine A(2A) receptors (A(2A)Rs). The present work thus addressed the contribution of CP-AMPARs and A(2A)Rs to i-LTP, which was induced in rat hippocampal slices by brief (10 min) oxygen/glucose deprivation (OGD). The amplitude of afferent-evoked excitatory postsynaptic currents (EPSCs) recorded from CA1 pyramidal neurons was decreased during OGD but gradually recovered toward values significantly above (157 +/- 17%) the baseline (100%) 40-50 min after re-oxygenation. This i-LTP was precluded by CP-AMPAR blockade (internal spermine (500 mu M) or extracellular NASPM (20 mu M) application) as well as by A(2A)R blockade with a selective antagonist (SCH 58261, 100 nM). OGD prompted sustained (>70 min) facilitation of mEPSC amplitude and frequency, and decreased mEPSC decay time, all of which were prevented by SCH 58261 (100 nM). The ability of NASPM (20 mu M) to acutely inhibit EPSCs 1 h after OGD, but not in control conditions nor in OGD-challenged slices when in the presence of SCH 58261 (100 nM), further supports sustained CP-AMPAR recruitment by i-LTP in an A(2A)R-dependent way. We propose that although i-LTP may initially mimic LTP, failure of auto-regulated CP-AMPAR removal from synapses could constitute an early divergent event between these forms of plasticity. (C) 2012 Elsevier Ltd. All rights reserved.
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