A novel role for calcium-independent phospholipase A2 in α-amino-3-hydroxy-5-methylisoxazole-propionate receptor regulation during long-term potentiation

Marc André Martel, Christian Patenaude, Caroline Ménard, Stéphanie Alaux, Brian S. Cummings, Guy Massicotte

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16 Scopus citations

Abstract

A considerable body of evidence indicates that phospholipase A2 (PLA2) enzymes participate in long-term potentiation (LTP) of excitatory synaptic transmission. In the present study, we have undertaken experiments to identify which calcium-independent isoform of PLA2 is involved in synaptic plasticity and to determine whether calcium-independent PLA2 (iPLA2) contributes to post-synaptic processes of LTP. Using field recordings from rat CA1 hippocampal slices, we found that theta-burst stimulation (TBS)-induced LTP of field excitatory post-synaptic potentials (fEPSPs) was abolished by the iPLA2 inhibitor bromoenol lactone (BEL) but not by the Ca2+-dependent PLA2 inhibitor arachidonyl trifluoromethyl ketone (AACOCF3). The ionic currents generated during TBS were not affected during iPLA2 inhibition as BEL by itself had no effect on the magnitude of facilitation during burst responses. In addition, (R)-BEL, an enantioselective inhibitor of iPLA 2γ, precluded TBS-induced LTP, an action that was not replicated by the iPLA2β inhibitors (S)-BEL and methyl arachidonyl fluorophosphonate. (R)-BEL was, however, ineffective on pre-established LTP. Finally, BEL also prevented the potentiation of fEPSPs elicited by brief exposure to 50 μM N-methyl-d-aspartate, as well as the associated up-regulation of α-amino-3-hydroxy-5-methylisoxazole-propionate (AMPA) receptor GluR1 subunit levels and the increase of 3H-AMPA binding in crude synaptic fractions. Collectively, these results unravel a new role for iPLA2γ in LTP, which appears to favor the insertion of AMPA receptors at post-synaptic membranes.

Original languageEnglish
Pages (from-to)505-513
Number of pages9
JournalEuropean Journal of Neuroscience
Volume23
Issue number2
DOIs
StatePublished - Jan 2006
Externally publishedYes

Keywords

  • Field excitatory post-synaptic potentials
  • Hippocampus
  • Phospholipase A inhibitors
  • Rat
  • Synaptic plasticity

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