title: Impaired corticostriatal LTP and depotentiation following iPLA2 inhibition is restored following acute application of DHA.
abstract: Docosahexaenoic acid (DHA) is a 22 carbon, six cis-double bonded (22:6, w3) omega-3 polyunsaturated acid (PUFA), found highly enriched with neuronal membranes, and believed to play a critical role in synaptic plasticity and cognitive correlates of learning and memory. DHA is released from the neuronal membrane via the action of the cytostolic calcium-independent phospholipase A2 (iPLA2) enzyme. Previous studies have demonstrated that inhibition of iPLA2 by bromoenol lactone (BEL), results in inhibition of CA1 long-term potentiation (LTP), restored following acute application of DHA. In the present study, we investigated the effect of selective iPLA2 inhibition and acute application of DHA on corticostriatal synaptic plasticity. We demonstrate that acute application of 30μM DHA facilitates cotricostriatal LTP, whilst long-term depression (LTD), basal transmission, and paired-pulse facilitation (PPF) are unaffected. Conversely, selective inhibition of iPLA2, via acute application of 10μM BEL, inhibits the expression of corticostriatal LTP, with no effect on LTD. Furthermore, we show that 10μM BEL inhibition of LTP is reversed following acute application of 30μM DHA. Finally, we demonstrate that 10μM BEL inhibits depotentiation of corticostriatal LTP, which is restored following acute application of 30μM DHA. Our findings indicate that appropriate release of DHA is a critical facet of corticostriatal LTP and depotentiation, and thus provides an exciting cellular target for the positive facilitation of cognitive function observed following DHA dietary supplementation.
authors.affiliation: School of Life Sciences, Faculty of Natural Sciences, Keele University, Keele, Staffordshire ST5 5BG, United Kingdom. Electronic address: d.mazzocchi-jones@keele.ac.uk.
authors.forename: David
authors.initials: D
authors.lastname: Mazzocchi-Jones
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology*; D003342:Corpus Striatum / Q000187:drug effects / Q000502:physiology*; D004281:Docosahexaenoic Acids / Q000494:pharmacology / Q000502:physiology*; D004558:Electric Stimulation; D054522:Group VI Phospholipases A2 / Q000037:antagonists & inhibitors / Q000502:physiology*; D017774:Long-Term Potentiation / Q000187:drug effects; D036881:Long-Term Synaptic Depression / Q000187:drug effects; D051379:Mice; D009281:Naphthalenes / Q000494:pharmacology; D011753:Pyrones / Q000494:pharmacology
chemical_list: D009281:Naphthalenes; D011753:Pyrones; D004281:Docosahexaenoic Acids; C068314:6-(bromomethylene)tetrahydro-3-(1-naphthaleneyl)-2H-pyran-2-one; D054522:Group VI Phospholipases A2; C516476:Pla2g6 protein, mouse
keywords: Depotentiation; Docosahexaenoic acid; Omega-3; Striatum; Synaptic plasticity