Lipid signaling in cytosolic phospholipase A2alpha-cyclooxygenase-2 cascade mediates cerebellar long-term depression and motor learning.

Proceedings of the National Academy of Sciences of the United States of America
Tung Dinh LeMasao Ito

Abstract

In this study, we show the crucial roles of lipid signaling in long-term depression (LTD), that is, synaptic plasticity prevailing in cerebellar Purkinje cells. In mouse brain slices, we found that cPLA(2)alpha knockout blocked LTD induction, which was rescued by replenishing arachidonic acid (AA) or prostaglandin (PG) D(2) or E(2). Moreover, cyclooxygenase (COX)-2 inhibitors block LTD, which is rescued by supplementing PGD(2)/E(2). The blockade or rescue occurs when these reagents are applied within a time window of 5-15 min following the onset of LTD-inducing stimulation. Furthermore, PGD(2)/E(2) facilitates the chemical induction of LTD by a PKC activator but is unable to rescue the LTD blocked by a PKC inhibitor. We conclude that PGD(2)/E(2) mediates LTD jointly with PKC, and suggest possible pathways for their interaction. Finally, we demonstrate in awake mice that cPLA(2)alpha deficiency or COX-2 inhibition attenuates short-term adaptation of optokinetic eye movements, supporting the view that LTD underlies motor learning.

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Citations

Oct 7, 2011·The Cerebellum·Elizabeth A FinchGeorge J Augustine
Dec 1, 2010·Nature Reviews. Endocrinology·Tomoyuki Furuyashiki, Shuh Narumiya
Oct 1, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·David T Stark, Nicolas G Bazan
Dec 2, 2015·Proceedings of the National Academy of Sciences of the United States of America·Liang ZhouYing Shen
Nov 28, 2012·Neural Networks : the Official Journal of the International Neural Network Society·Taegon Kim, Keiko Tanaka-Yamamoto
Mar 5, 2015·Proceedings of the National Academy of Sciences of the United States of America·Tadashi YamazakiShigeru Tanaka
Apr 16, 2014·Frontiers in Systems Neuroscience·Richard Hawkes
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Aug 24, 2016·Proceedings of the National Academy of Sciences of the United States of America·Kazuhiko YamaguchiMasao Ito
Apr 4, 2015·Journal of Lipid Research·Christina C Leslie
Nov 14, 2017·Proceedings of the Japan Academy. Series B, Physical and Biological Sciences·Makoto Murakami
Jul 19, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Pei-Pei Guan, Pu Wang
Jun 4, 2020·Journal of Lipid Research·Takeshi Harayama, Takao Shimizu

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