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

First Author  Le TD Year  2010
Journal  Proc Natl Acad Sci U S A Volume  107
Issue  7 Pages  3198-203
PubMed ID  20133605 Mgi Jnum  J:157576
Mgi Id  MGI:4431142 Doi  10.1073/pnas.0915020107
Citation  Le TD, et al. (2010) Lipid signaling in cytosolic phospholipase A2alpha-cyclooxygenase-2 cascade mediates cerebellar long-term depression and motor learning. Proc Natl Acad Sci U S A 107(7):3198-203
abstractText  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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